Ryohei Takeuchi

The purpose of this study was to determine the frequency of lateral hinge fractures after opening-wedge high tibial osteotomy and investigate the patterns of fracture and their clinical outcome.We analyzed 104 knees in 93 patients with a mean age of 68 ± 7 years. Of the knees, 74 were diagnosed as having primary osteoarthritis and 30 with osteonecrosis. The mean follow-up period was 41 months. Lateral hinge fractures were classified as follows: type I, the fracture reaches just proximal to or within the tibiofibular joint; type II, the fracture reaches the distal portion of the proximal tibiofibular joint; and type III, a lateral plateau fracture. A standard postoperative rehabilitation protocol was used for type I fractures, 3 of 5 patients with type II fractures were treated with non-weight bearing, and type III fractures were treated with non-weight bearing until visible callus formation.The Knee Society scores for the knee and for function showed improvement from 49 ± 11 to 91 ± 7.7 points and from 62 ± 13 to 95 ± 8.2 points, respectively. Lateral cortex fractures were observed in 26 knees (25%): 19 type I, 5 type II, and 2 type III. In the type II fracture group, 2 of 5 patients were judged to have a delayed bone union. There were 2 cases of infection (2%) and 1 case of traumatic neuroma (1%) but no instances of implant failure, nonunion, or deep vein thrombosis among our patient cohort.High tibial osteotomy patients treated with a combination of TomoFix (Synthes, Bettlach, Switzerland) and bone substitute were able to walk with full weight bearing 2 weeks after surgery. No complications were seen in 19 patients with type I fractures. Of 5 patients with type II fractures, 2 had delayed unions with a correction loss of 3° and 7°, respectively.Level IV, therapeutic case series.

PurposeThe purposes of this study were to evaluate regeneration of the articular cartilage after medial opening-wedge high tibial osteotomy for knees with medial-compartment osteoarthritis and to assess the clinical outcome and cartilage regeneration according to the postoperative limb alignment at 2 years postoperatively.MethodsThe study involved 159 knees in 159 patients. For evaluation of cartilage degeneration, the International Cartilage Repair Society grading system was used for arthroscopic grading on initial arthroscopy during high tibial osteotomy. The patients underwent a second-look arthroscopic evaluation of the articular cartilage at the time of removal of the plate, an average of 2 years after the initial osteotomy. For evaluation of cartilage regeneration, the articular cartilage was classified into 2 stages as no regenerative change (grade 1) or white scattering with fibrocartilage, partial coverage with fibrocartilage, or even coverage with fibrocartilage (grade 2) on second-look arthroscopy. Maturation of the cartilage regeneration was defined as even coverage with fibrocartilage. “Immaturation” of the cartilage regeneration was defined as white scattering with fibrocartilage or partial coverage with fibrocartilage. Clinical evaluations were performed by use of Knee Society scores preoperatively and at 2 years postoperatively. We divided the knees into 3 groups according to the postoperative limb alignment. Group A comprised knees with a mechanical tibiofemoral angle of 0° or less. Group B comprised knees with a mechanical tibiofemoral angle greater than 0° and less than 6°. Group C comprised knees with a mechanical tibiofemoral angle of 6° or greater.ResultsGrade 2 regeneration was achieved in the medial femoral condyle articular cartilage in 92% of knees and in the medial tibial plateau articular cartilage in 69% of knees. Maturation of the cartilage regeneration was found in the medial femoral condyle articular cartilage in 4% of knees and in the medial tibial plateau articular cartilage in 1% of knees. At follow-up, no significant differences were seen between clinical outcomes and initial cartilage degeneration (P = .338) or cartilage regeneration (P = .699). Regeneration of the medial femoral condyle articular cartilage was found in 75% of group A knees, 95% of group B knees, and 92% of group C knees. Significant differences were seen between cartilage regeneration and clinical outcomes (P = .001), as well as postoperative limb alignment (P = .018). Clinical and regeneration results were better in group B than in groups A and C.ConclusionsThe degenerated cartilage of the medial femoral condyle and medial tibial plateau could be partially or entirely covered by newly regenerated cartilage at 2 years after adequate correction of varus deformity by medial opening-wedge high tibial osteotomy without cartilage regeneration strategies.Level of EvidenceLevel IV, therapeutic case series. The purposes of this study were to evaluate regeneration of the articular cartilage after medial opening-wedge high tibial osteotomy for knees with medial-compartment osteoarthritis and to assess the clinical outcome and cartilage regeneration according to the postoperative limb alignment at 2 years postoperatively. The study involved 159 knees in 159 patients. For evaluation of cartilage degeneration, the International Cartilage Repair Society grading system was used for arthroscopic grading on initial arthroscopy during high tibial osteotomy. The patients underwent a second-look arthroscopic evaluation of the articular cartilage at the time of removal of the plate, an average of 2 years after the initial osteotomy. For evaluation of cartilage regeneration, the articular cartilage was classified into 2 stages as no regenerative change (grade 1) or white scattering with fibrocartilage, partial coverage with fibrocartilage, or even coverage with fibrocartilage (grade 2) on second-look arthroscopy. Maturation of the cartilage regeneration was defined as even coverage with fibrocartilage. “Immaturation” of the cartilage regeneration was defined as white scattering with fibrocartilage or partial coverage with fibrocartilage. Clinical evaluations were performed by use of Knee Society scores preoperatively and at 2 years postoperatively. We divided the knees into 3 groups according to the postoperative limb alignment. Group A comprised knees with a mechanical tibiofemoral angle of 0° or less. Group B comprised knees with a mechanical tibiofemoral angle greater than 0° and less than 6°. Group C comprised knees with a mechanical tibiofemoral angle of 6° or greater. Grade 2 regeneration was achieved in the medial femoral condyle articular cartilage in 92% of knees and in the medial tibial plateau articular cartilage in 69% of knees. Maturation of the cartilage regeneration was found in the medial femoral condyle articular cartilage in 4% of knees and in the medial tibial plateau articular cartilage in 1% of knees. At follow-up, no significant differences were seen between clinical outcomes and initial cartilage degeneration (P = .338) or cartilage regeneration (P = .699). Regeneration of the medial femoral condyle articular cartilage was found in 75% of group A knees, 95% of group B knees, and 92% of group C knees. Significant differences were seen between cartilage regeneration and clinical outcomes (P = .001), as well as postoperative limb alignment (P = .018). Clinical and regeneration results were better in group B than in groups A and C. The degenerated cartilage of the medial femoral condyle and medial tibial plateau could be partially or entirely covered by newly regenerated cartilage at 2 years after adequate correction of varus deformity by medial opening-wedge high tibial osteotomy without cartilage regeneration strategies.

We performed clinical and radiographic evaluation of patients with medial compartment osteoarthritis of the knee who had undergone treatment with opening wedge high tibial osteotomy (OWHTO) followed by early full weight bearing. OWHTO procedures were performed by use of TomoFix (Synthes, Bettlach, Switzerland) and bone substitute materials.OWHTO was performed in 57 knees in 52 patients with a mean age of 69 years (range, 54 to 82 years) at the time of operation. The diagnosis was primary osteoarthritis in 34 knees in 29 patients and osteonecrosis in a further 23 knees in 23 patients. We established an early weight-bearing exercise program during which these patients were permitted partial weight-bearing exercise 1 week after their osteotomy procedure. All patients performed full weight-bearing exercises at 2 weeks after surgery. The mean follow-up period was 40 months (range, 24 to 62 months).The American Knee Society Score and Function Score showed significant improvement from 50.9 +/- 12.3 to 91.7 +/- 6.9 points and 59.3 +/- 13.1 to 94.1 +/- 8.8 points, respectively. Before surgery, the mean femorotibial angle during standing was 181.3 degrees +/- 2.4 degrees (1.3 degrees anatomic varus), but it measured 169.6 degrees +/- 2.3 degrees (10.4 degrees valgus) at the time of follow-up. There were no instances of nonunion or implant failure in any of our patients.We have shown that an early weight-bearing exercise program enables full weight bearing at 2 weeks after OWHTO with TomoFix and artificial bone wedges. Overall, this combination was a highly successful course of treatment for correcting knee malalignment in patients with medial compartment osteoarthritis.Level IV, therapeutic case series.

In Japan, only few cross-culturally adapted, internationally used orthopaedic patient self-assessed outcome scores are available. In addition, the high incidence of knee osteoarthritis (OA) suggests the need for validated outcome measures such as the widely used Knee Injury and Osteoarthritis Outcome Score (KOOS) for Japanese populations. The purpose of this study was to provide a cross-culturally adapted and validated KOOS questionnaire for further use in national and international clinical projects involving Japanese patients.The Japanese KOOS was developed according to the standard cross-cultural adaptation guidelines. For validation, the KOOS was tested on 58 patients diagnosed with OA. Reliability was tested using the intraclass correlation coefficient (ICC). Internal consistency or homogeneity was assessed using Cronbach's alpha. Construct validity was evaluated by quantifying the correlation between the KOOS and the Japanese OKS and SF-36 questionnaires with Spearmann's correlation coefficients.No major difficulties were encountered during the translation and pre-testing stages. All five KOOS subscales showed adequate reproducibility with ICC values greater than 0.85, high internal consistency with Cronbach's alpha values around 0.90, and high Spearmann's coefficients over 0.50 signifying good correlation between the KOOS subscales and the OKS as well as the majority of the established subscales of the SF-36. No floor and ceiling effects were observed for the five subscales.Our validated Japanese KOOS is a reliable and stable outcomes measure that provides a valuable basis for national and international clinical projects focusing on patient-based assessments in knee OA.

The effect of low-intensity pulsed ultrasound (LIPUS) on cell growth was examined in three-dimensional-cultured chondrocytes with a collagen sponge. To elucidate the mechanisms underlying the mechanical activation of chondrocytes, intracellular signaling pathways through the Ras/mitogen-activated protein kinase (MAPK) and the integrin/phosphatidylinositol 3 kinase (PI3K)/Akt pathways as well as proteins involved in proliferation of chondrocytes were examined in LIPUS-treated chondrocytes.Articular cartilage tissue was obtained from the metatarso-phalangeal joints of freshly sacrificed pigs. Isolated chondrocytes mixed with collagen gel and culture medium composites were added to type-I collagen honeycomb sponges. Experimental cells were cultured with daily 20-minute exposures to LIPUS. The chondrocytes proliferated and a collagenous matrix was formed on the surface of the sponge. Cell counting, histological examinations, immunohistochemical analyses and western blotting analysis were performed.The rate of chondrocyte proliferation was slightly but significantly higher in the LIPUS group in comparison with the control group during the 2-week culture period. Western blot analysis showed intense staining of type-IX collagen, cyclin B1 and cyclin D1, phosphorylated focal adhesion kinase, and phosphorylated Akt in the LIPUS group in comparison with the control group. No differences were detected, however, in the MAPK, phosphorylated MAPK and type-II collagen levels.LIPUS promoted the proliferation of cultured chondrocytes and the production of type-IX collagen in a three-dimensional culture using a collagen sponge. In addition, the anabolic LIPUS signal transduction to the nucleus via the integrin/phosphatidylinositol 3-OH kinase/Akt pathway rather than the integrin/MAPK pathway was generally associated with cell proliferation.

<h2>Abstract</h2> High tibial valgus osteotomy (HTO) is an established treatment for medial-compartment osteoarthritis of the knee. We have combined medial open and lateral closed-wedge HTO (hybrid closed-wedge HTO) to overcome the limitations of traditional closed-wedge HTO. Our new hybrid procedure has the following advantages: (1) the bone block removed is smaller in size; (2) the procedure yields optimal geometric characteristics for bone healing; (3) there is no step-off at the lateral osteotomy site; (4) the lateral cortex of the proximal and distal fragments is attached firmly by the oblique osteotomy; and (5) early full weight-bearing walking is possible. This procedure is effective in treating medial-compartment osteoarthritis accompanied by patellofemoral osteoarthritis. The indications for this procedure include a willingness and ability to comply with the postoperative rehabilitation program; a diagnosis of either medial-compartment osteoarthritis or complicated patellofemoral osteoarthritis; and preferably, an age of 70 years or younger, although this is not a strict constraint. Patients are permitted to stand using both legs on the day after surgery and walk with full weight bearing within 2 weeks of undergoing our novel HTO procedure. We describe the details of this surgical technique and the postoperative rehabilitation program for the patients who undergo this treatment.

The purposes of this study were to compare the results of medial opening-wedge high tibial osteotomy (MOWHTO) with and without subchondral drilling and to assess the formation of fibrocartilage at 2 years postoperatively.Patients were divided into 2 groups. Thirty knees were treated with osteotomy and subchondral drilling (group 1), and 31 knees were treated with osteotomy alone (group 2). Clinical evaluations were performed by use of Knee Society scores preoperatively and at 2 years postoperatively. For evaluation of cartilage degeneration, the International Cartilage Repair Society grading system was used for arthroscopic grading on initial arthroscopy during high tibial osteotomy. The patients underwent a second-look arthroscopic evaluation of the articular cartilage at the time of removal of the plate, an average of 2 years after the initial osteotomy. For evaluation of formation of fibrocartilage on second-look arthroscopy, the articular cartilage was classified as having either no change from initial surgery (grade I) or white scattering with fibrocartilage, partial coverage with fibrocartilage, or even coverage with fibrocartilage (grade II). In addition, maturation of the appearance of the cartilage was defined. The appearance was considered mature if the chondral defects were evenly covered with fibrocartilage. It was considered immature if there was white scattering or only partial coverage with fibrocartilage.In group 1 the mean Knee Society knee score and function score were 67.3 ± 8.2 points and 66.5 ± 14.3 points, respectively, preoperatively. At 2 years postoperatively, they improved to 91.2 ± 6.4 and 92.8 ± 10.0, respectively (P = .001 and P = .001, respectively). In group 2 the mean Knee Society knee score and function score were 63.7 ± 13.9 points and 66.8 ± 9.1 points, respectively, preoperatively. At 2 years postoperatively, they improved to 92.5 ± 5.3 points and 92.2 ± 8.0 points, respectively (P = .001 and P = .001, respectively). There were no significant differences in the postoperative Knee Society knee score and function score at 2 years' follow-up between the groups (P = .389 and P = .806, respectively). Grade II regeneration was achieved in the medial femoral condyle articular cartilage in 100% of knees in group 1 and 94% of knees in group 2 (P = .492). Maturation of the cartilage was found in the medial femoral condyle articular cartilage in 10% of knees in group 1 and 3% of knees in group 2 (P = .354). There was no significant difference in the formation of fibrocartilage between the groups.Subchondral drilling had no effect on the outcome at 2 years after MOWHTO. In addition, there was no significant difference in the formation of fibrocartilage with or without subchondral drilling. Therefore subchondral drilling is not necessary after MOWHTO.Level III, retrospective comparative study.

The bone-hamstring-bone (BHB) composite graft is a hybrid ligament reconstruction methodology that combines the advantages but eliminates the disadvantages of the bone-patellar tendon-bone (BPTB) and tendon of semitendinosus and gracilis muscle (STG) methods. We have developed an innovative modified BHB method involving anatomic anterior cruciate ligament (ACL) reconstruction. It takes into account the 2 bundles of the ACL: the anteromedial bundle and the posterolateral bundle. The composite graft was prepared by folding the gracilis and the semitendinosus tendons twice and flanking the ends by bone blocks obtained from the tibia. One tunnel of 11-mm diameter was made in the tibia and the femur, and the top of the graft was introduced into the femoral socket; the distal end of the graft was rotated 90° in the counterclockwise direction for a right knee and 90° in the clockwise direction for a left knee to apply a twist to the graft, giving rise to an anteromedial bundle and a posterolateral bundle. The bone blocks attached to the graft were fixed with 2 interference screws. Modified BHB technique allows free selection of the location of the bone plug, minimizes the intra-articular length of the graft, and maintains the double-bundle structure of the original ACL. Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 18, No 5 (May-June), 2002: pp 550–555

The choice of surgical treatments for unicompartmental osteoarthritis (OA) of the knee is still somewhat controversial. Midterm results from cases treated using unicompartmental knee arthroplasty (UKA) or open wedge high tibial osteotomy (OWHTO) were evaluated retrospectively.Twenty-seven knees of 24 patients with varus deformities underwent OWHTO and 30 knees of 18 patients underwent UKA surgeries for the treatment of medial compartmental osteoarthritis (OA). The KSS score, FTA, range of motion and complications were evaluated before and after surgery.The preoperative mean KSS scores were 49 points in the OWHTO group and 62 in the UKA group which improved postoperatively to 89 (excellent; 19 knees, good; 8 knees), and 88 (excellent; 25, good; 4, fair; 1), respectively. There was no significant difference between the OWHTO and UKA scores. Seventeen patients in the OWHTO group could sit comfortably in the formal Japanese style after surgery. The preoperative mean FTA values for the OWHTO and UKA groups were 182 degrees and 184, and at follow-up measured 169 and 170, respectively. In the UKA group, the femoral component and the polyethylene insertion in one patient was exchanged at 5 years post-surgery and revision TKAs were performed in 2 cases. In the OWHTO group, one tibial plateau fracture and one subcutaneous tissue infection were noted.Treatment options should be carefully considered for each OA patient in accordance with their activity levels, grade of advanced OA, age, and range of motion of the knee. OWHTO shows an improved indication for active patients with a good range of motion of the knee.

Abstract We investigated the effect of low‐intensity pulsed ultrasound (LIPUS) on the homing of circulating osteogenic progenitors to the fracture site. Parabiotic animals were formed by surgically conjoining a green fluorescent protein (GFP) mouse and a syngeneic wild‐type mouse. A transverse femoral fracture was made in the contralateral hind limb of the wild‐type partner. The fracture site was exposed to daily LIPUS in the treatment group. Animals without LIPUS treatment served as the control group. Radiological assessment showed that the hard callus area was significantly greater in the LIPUS group than in the control group at 2 and 4 weeks post‐fracture. Histomorphometric analysis at the fracture site showed a significant increase of GFP cells in the LIPUS group after 2 weeks (7.5%), compared to the control group (2.4%) ( p &lt; 0.05). The LIPUS group exhibited a significantly higher percentage of GFP cells expressing alkaline phosphatase (GFP/AP) than the control group at 2 weeks post‐fracture (5.9%, 0.3%, respectively, p &lt; 0.05). There was no significant difference in the percentage of GFP/AP cells between the LIPUS group (2.0%) and the control group (1.4%) at 4 weeks post‐fracture. Stromal cell derived factor‐1 and CXCR4 were immunohistochemically identified at the fracture site in the LIPUS group. These data indicate that LIPUS induced the homing of circulating osteogenic progenitors to the fracture site for possible contribution to new bone formation. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1516–1521, 2012

It has been predicted that significant stress will be applied to the plate and lateral cortical hinge of an osteotomy site when early full weight bearing is commenced after an open wedge high tibial osteotomy. We hypothesized that the stress concentration on the plate or at the lateral cortical hinge would be reduced by inserting bone substitutes into the osteotomy gap. Two different types of tibia model were investigated: Group A, fixation with TomoFix with the osteotomy site left as an open space; and Group B, two β-TCP wedges are inserted into osteotomy site and fixed with TomoFix. Stress at five points was measured using strain gauges. Specimens were mounted onto a testing machine with an FTA (femoro-tibial angle) of 170°. Cyclic load tests and an ultimate load test were then performed. The mean stress on the plate was measured at 15.5±1.8 Mpa in Group A. On the other hand, this value in Group B was only 9.52±2.1 Mpa and this was a significant difference (P<0.01). The mean stress on the lateral hinge in Groups A and B was 3.31±0.5 and 2.49±0.2, respectively which was also a significant difference (P<0.05). The mean maximum breaking load in Group A was 2500±280 N and in Group B 4270±420 N which was a significant difference (P<0.01). Hence, for OWHTO procedures, the use of β-TCP wedges and TomoFix is thus likely to improve the initial axial and possibly rotational stability at the osteotomy site in comparison with methods that leave the osteotomy gap open.

Journal of Tissue Engineering and Regenerative MedicineVolume 10, Issue 8 p. 700-710 Research Article In vivo vascularization of cell sheets provided better long-term tissue survival than injection of cell suspension Ryohei Takeuchi, Ryohei Takeuchi Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), Tokyo, Japan Terumo Corporation, Research and Development Headquarters, Kanagawa, Japan Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, JapanSearch for more papers by this authorYosuke Kuruma, Yosuke Kuruma Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), Tokyo, Japan Terumo Corporation, Research and Development Headquarters, Kanagawa, JapanSearch for more papers by this authorHidekazu Sekine, Hidekazu Sekine Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), Tokyo, JapanSearch for more papers by this authorIzumi Dobashi, Izumi Dobashi Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), Tokyo, JapanSearch for more papers by this authorMasayuki Yamato, Masayuki Yamato Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), Tokyo, JapanSearch for more papers by this authorMitsuo Umezu, Mitsuo Umezu Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, JapanSearch for more papers by this authorTatsuya Shimizu, Tatsuya Shimizu Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), Tokyo, JapanSearch for more papers by this authorTeruo Okano, Corresponding Author Teruo Okano Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), Tokyo, JapanCorrespondence to: Teruo Okano, Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), 8–1 Kawada-cho, Shinjuku-ku, Tokyo 162–8666, Japan. E-mail: tokano@abmes.twmu.ac.jpSearch for more papers by this author Ryohei Takeuchi, Ryohei Takeuchi Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), Tokyo, Japan Terumo Corporation, Research and Development Headquarters, Kanagawa, Japan Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, JapanSearch for more papers by this authorYosuke Kuruma, Yosuke Kuruma Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), Tokyo, Japan Terumo Corporation, Research and Development Headquarters, Kanagawa, JapanSearch for more papers by this authorHidekazu Sekine, Hidekazu Sekine Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), Tokyo, JapanSearch for more papers by this authorIzumi Dobashi, Izumi Dobashi Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), Tokyo, JapanSearch for more papers by this authorMasayuki Yamato, Masayuki Yamato Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), Tokyo, JapanSearch for more papers by this authorMitsuo Umezu, Mitsuo Umezu Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, JapanSearch for more papers by this authorTatsuya Shimizu, Tatsuya Shimizu Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), Tokyo, JapanSearch for more papers by this authorTeruo Okano, Corresponding Author Teruo Okano Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), Tokyo, JapanCorrespondence to: Teruo Okano, Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), 8–1 Kawada-cho, Shinjuku-ku, Tokyo 162–8666, Japan. E-mail: tokano@abmes.twmu.ac.jpSearch for more papers by this author First published: 28 January 2014 https://doi.org/10.1002/term.1854Citations: 24Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Cell sheets have shown a remarkable ability for repairing damaged myocardium in clinical and preclinical studies. Although they demonstrate a high degree of viability as engrafted cells in vivo, the reason behind their survivability is unclear. In this study, the survival and vascularization of rat cardiac cell sheets transplanted in the subcutaneous tissue of athymic rats were investigated temporally. The cell sheets showed significantly higher survival than cell suspensions for up to 12 months, using an in vivo bioluminescence imaging system to detect luciferase-positive transplanted cells. Terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay also showed a smaller number of apoptotic cells in the cell sheets than in the cell suspensions at 1 day. Rapid vascular formation and maturation were observed inside the cell sheets using an in vivo imaging system. Leaky vessels appeared at 6 h, red blood cells flowing through functional vessels appeared at 12 h, and morphologically matured vessels appeared at 7 days. In addition, immunostaining of cell sheets with nerve/glial antigen-2 (NG2) showed that vessel maturity increased over time. Interestingly, these results correlated with the dynamics of cell sheet mRNA expression. Genes related to endothelial cells (ECs) proliferation, migration and vessel sprouting were highly expressed within 1 day, and genes related to pericyte recruitment and vessel maturation were highly expressed at 3 days or later. This suggested that the cell sheets could secrete appropriate angiogenic factors in a timely way after transplantation, and this ability might be a key reason for their high survival. Copyright © 2014 John Wiley & Sons, Ltd. Citing Literature Volume10, Issue8August 2016Pages 700-710 RelatedInformation

Open-wedge high tibial osteotomy is considered to be an effective surgical intervention for medial compartmental knee osteoarthritis. However, patella infra, which has been reported to be a result of tuberosity distalization after open-wedge high tibial osteotomy, changes the native patellofemoral biomechanics. This could raise abnormal patellofemoral contact stresses, which might be the trigger of patellofemoral arthrosis. To minimize the reduction in patellar height, we have developed a technique called open-wedge distal tuberosity tibial osteotomy. The benefits of this technique include increased bone-to-bone contact of the distal tuberosity cut surface after correction by cutting an arc osteotomy around the hinge position, which is the center of rotation. This technique also provides cortical support at the anterior osteotomy site without additional bone defect and, therefore, may be advantageous against weight-bearing stress on the osteotomy site. In all, open-wedge distal tuberosity tibial osteotomy could potentially be a unique open-wedge osteotomy that eliminates the risk for postoperative patellofemoral osteoarthritis and also could theoretically encourage rapid healing of the osteotomy, which could lead to early return to full physical activity.

Using the LET distribution obtained by CR-39 plastic track detectors and the total absorbed dose obtained by TLDs, whose response for relativistic heavy ions is proportional to the absorbed dose, the dose equivalents at various locations inside the Space Shuttle (STS-47) have been estimated. The results show a large difference in the effective quality factor compared with the results obtained from a tissue equivalent proportional counter. The reason for this discrepancy is discussed.

The treatment of patients with osteoarthritic knees accompanied by ipsilateral osteoarthritic ankles is not well documented. We here report both clinical results and radiographic evaluations of such patients treated using a high tibial osteotomy (HTO). HTO was performed on 16 knees of 10 patients (all women with a mean age; 68 years; range 58 to 73 years) who had a varus deformity of both their legs as a result of medial compartmental osteoarthritis of their knees. The Hospital for Special Surgery's (HSS score) knee scoring system and the clinical rating system for the ankle-hindfoot by Kitaoka (AOFAS) were used to evaluate the patients clinically before and after HTO. Radiographic findings were measured using antero-posterior one-leg weight bearing radiographs of the whole lower extremity taken before surgery. The mean time of follow-up was 8 years (range, 4-10 years). The HSS score improved from 54 to 91 points after HTO and the mean ankle score improved significantly from 54 to 86 points. After HTO also, the alignment of the knees changed from 6 degrees varus to 12 degrees valgus. The decrease of the inclination angle of the tibial axis changed from 10 degrees laterally to - 2 degrees medially and the talar tilt angle improved from 18 degrees to 6 degrees resulting in an improvement of the ankle congruity. HTO, which can correct the total alignment of the lower extremity, is thus recommended as one of more effective surgical procedures for patients with an ipsilateral osteoarthritis of the knee and ankle.

The Achilles tendon was implanted into a bone tunnel made in the femoral condyle of 20 rabbits. In the left femur, collagen gel mixed with hydroxyapatite powder (C-HAp) was injected between the graft and the bone tunnel. On the other hand, as a control, simple saline was injected in the right femur. Five rabbits were sacrificed at 4, 8, 12, and 16 weeks after surgery. Histological findings showed that in the C-HAp group, the grafted tendon came in direct contact with new bone, and Sharpey-like collagen fibers arising from the grafted tendon were observed to penetrate new bone by 4 weeks after surgery. In the control group, however, fibrous tissue was observed between new bone and the grafted tendon, but no penetrating fibers from the grafted tendon into the new bone were observed until 16 weeks. The area of new bone in the C-HAp group was significantly greater than that in the control group 4, 8, and 12 weeks after surgery (p < 0.0001, p < 0.0007, p < 0.0013, respectively).

The purpose of this study was to compare the mechanical fixation strengths of anteromedial and medial plate positions in osteotomy, and clarify the effects of bone substitute placement into the osteotomy site.Twenty-eight sawbone tibia models were used. Four different models were prepared: Group A, the osteotomy site was open and the plate position was anteromedial; Group B, bone substitutes were inserted into the osteotomy site and the plate position was anteromedial; Group C, the osteotomy site was open and the plate position was medial; and Group D, bone substitutes were inserted into the osteotomy site and the plate position was medial. The loading condition ranged from 0 to 800N and one hertz cycles were applied. Changes of the tibial posterior slope angle (TPS), stress on the plate and lateral hinge were measured.The changes in the TPS and the stress on the plate were significantly larger in Group A than in Group C. These were significantly larger in Group A than in Group B, and in Group C than in Group D. There was no significant difference between Group B and Group D, and no significant difference between knee flexion angles of 0° and 10°. Stress on the lateral hinge was significantly smaller when bone substitute was used.A medial plate position was biomechanically superior to an anteromedial position if bone substitute was not used. Bone substitute distributed the stress concentration around the osteotomy gap and prevented an increase in TPS angle regardless of the plate position.

Although antibiotic-loaded hydroxyapatite blocks have been used for the treatment of chronic osteomyelitis, their long-term potential for releasing antibiotic into human bones is not well known. Five patients with chronic osteomyelitis due to methicillin-resistant Staphylococcus aureus (MRSA) infection were effectively treated with local implantation of vancomycin-loaded hydroxyapatite blocks. Blocks were removed during the following reconstructive surgeries when the releasing capability of the blocks, and the bacteriocidal activity of the remaining vancomycin in these blocks could be evaluated. Vancomycin was rapidly released within 1 month after implantation, and by 3 months 90% of vancomycin had leaked from the blocks. At 18 months vancomycin still remained in a bacteriocidal form in the hydroxyapatite blocks, though the blocks had no releasing potential or the eluted vancomycin had been changed to a different form. Vancomycin-loaded porous hydroxyapatite blocks would be useful for the treatment of chronic osteomyelitis or implant-associated osteomyelitis due to MRSA.

To assess responsiveness of the Japanese Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Oxford Knee Score (OKS) in patients undergoing open-wedge HTO to treat knee osteoarthritis and/or osteonecrosis. Patients completed a set of questionnaires before HTO surgery (baseline) and 1 year after surgery. The questionnaires comprised the validated Japanese versions of the KOOS, the OKS, and the SF-36v2 and a visual analogue scale (VAS) for local knee pain and general pain. The treating surgeon completed the Japanese Orthopedic Association (JOA) score for osteoarthritic knees. The study included 119 patients aged 64.7 ± 8.3, 116 were followed at 1 year. 90 patients had knee osteoarthritis (OA) solely. 28 patients suffered from both OA and osteonecrosis (ON); one patient had ON only. Responsiveness to change was assessed using the effect size (ES) between the baseline and the 1-year postoperative assessment and standardized response mean. A distribution-based approach was used to determine the minimally detectable change (MDC95) for the KOOS subscales, and the OKS. All instruments demonstrated statistically significant changes between the preoperative assessments and one year after surgery. All changes showed an improvement in score, but the condition-specific measures revealed higher responsiveness than the generic measures. All KOOS subscales, the OKS, the local pain VAS, and the JOA score showed large ESs (ES > 1.24) and SRMs (SRM>1.04). At a 95% confidence level, the respective MDCs were 15.83, 18.94, 15.22, 18.99 and 17.23 for the KOOS-Pain, KOOS-Symptoms, KOOS-ADL, KOOS-Sport/Rec, and KOOS-QOL subscales, respectively. The MDC95 for the OKS was 8.29. Both, the KOOS and OKS are responsive for use in Japanese-speaking patients with knee osteoarthritis and/or osteonecrosis who are undergoing HTO.

Purpose: This prospective multicenter study evaluated patient reported outcomes (PROs) in individuals undergoing medial open-wedge high-tibial osteotomy (OWHTO) with plate stabilization compared to conservative care or no treatment. Methods: One hundred eighteen of 148 patients older than 40 years were elected for OWHTO with plate treatment. Thirty patients declined surgery and were followed as a conservative group. The primary outcome measure was the Knee Injury and Osteoarthritis Outcome Score (KOOS) at 2 years. Secondary measures included Oxford knee score, Western Ontario and McMaster Universities osteoarthritis index, range of motion (ROM), joint space width (JSW), femorotibial angle (FTA), and weight-bearing line ratio (WBLR). Results: Patient enrollment and baseline characteristics were heterogeneously distributed and led to group characteristics that were not comparable. Therefore, the comparison of the KOOS between the groups showing no differences must be treated with caution. In the OWHTO plate group, all PROs and the ROM significantly improved between baseline and 2-year follow-up. JSW remained stable in the OWHTO group. The FTA and WBLR significantly changed from a mean of 179.3 (95% confidence interval (CI): 178.7, 179.9) to 169.8 (95% CI: 169.2, 170.5) and from 23.1 (95% CI: 20.7, 25.5) to 62.4 (95% CI 59.0, 65.8), respectively. Treatment failure with conversion to total knee arthroplasty occurred in 1% of the OWHTO group; and in the conservative group, 10% converted to HTO or knee arthroplasty. Conclusions: OWHTO with plate leads to significant improvement of PROs and function 2 years after intervention and demonstrates reliable mechanical axis correction with subsequent shift of weight-bearing.

The aim of this study is to evaluate, by computed tomography (CT), whether different torsional changes occur in the tibia following a lateral closed wedge high tibial osteotomy (CWHTO) versus a medial open wedge high tibial osteotomy (OWHTO) procedure. It was hypothesized that the distal fragment of the tibia would show greater internal rotation after CWHTO.Thirty knees from 25 patients who underwent HTO were enrolled. Fifteen knees of 14 patients who underwent CWHTO and 15 knees of 11 patients who received OWHTO were match-paired. CT scans were taken before and three weeks after surgery. Rotational changes in the distal fragment of the tibia were assessed by measuring the tibial torsion angle (TTA).The mean TTA in the CWHTO group pre-operatively and postoperatively was +23.9° ± 7.8° and + 18.2° ± 7.0°, respectively. Internal rotation of the distal fragment of the tibia after CWHTO was -5.7 ± 3.3° (P < 0.001). In the OWHTO group, the mean TTA pre-operatively and postoperatively was +27.9° ± 6.9° and + 26.8 ± 7.7°, respectively, with no significant change in torsion observed (P > 0.05).The distal fragment of the tibia rotated internally after CWHTO but not after OWHTO.Level III: case-control study.

Four patients, aged 37-50 years, with chronic anterior cruciate ligament (ACL) deficiency, medial compartment osteoarthritis and varus deformity, underwent simultaneous arthroscopic ACL reconstruction and opening wedge high tibial osteotomy using the TomoFix fixation device and hydroxyapatite wedges. The simultaneous procedure allowed our patients to perform a full weight-bearing exercise at 4 weeks after surgery. At device removal and concomitant second-look arthroscopy, all patients had either a cyclops-like lesion or partial tears at the point of contact between the reconstructed ACL and intercondylar notch. Therefore, subsequent notchplasty or re-notchplasty was required. Because of the small number of patients, the results should be considered preliminary. Given our findings of graft morbidity caused by the corrected postoperative alignment, adequate intercondylar notchplasty should be performed at the initial operation.

This study aims to identify, whether knee OA progression is affected by the sMCL proximal tibial attachment status and probably is the first one trying to identify such association.90 OA knees and 80 normal knees were evaluated using radiographs and MRI for severity of OA knee (K-L grade), sMCL length (L), distance of distal tibial attachment of sMCL from tibial articular surface (I), MCL ratio (L/I) and proximal tibial attachment of sMCL, attached or detached.Mean age of the study population was 52.93 ± 19.52 years. 106 were female knees and 59 were male. Status of sMCL proximal tibial attachment had highly statistically significant negative correlation with severity of OA knee (p-value <0.001). The status of sMCL proximal tibial attachment shows statistically significant negative correlation with sMCL distal tibial attachment and significant positive correlation MCL ratio. But there was no significant correlation with sMCL length. Knees with lower MCL ratio (L/I) have significant higher grade of OA knee as they shows statistically significant negative correlation.Detached sMCL proximal tibial attachment is found to be a strong predictor of OA knee progression. Assessing the status of sMCL proximal tibial attachment will not only help the physician identifying medial stability of the knee, but also assist in planning therapy for the knee in question.

In order to obtain better range of motion in knees with osteoarthritis, medial and lateral parapatellar retinaculo-capsular release operations were performed at the time of high tibial osteotomy, with fixation using dual plating on medial compartmental knee osteoarthritis (29 knees) or spontaneous osteonecrosis of the medial femoral condyle (15 knees). At removal of the blade plate, 1 to 2 years after the initial osteotomy, the same release procedures were performed together with resection of adhesive soft tissue and resection of osteophytes, which were obstacles to full flexion. A grading system (Grade 0–3) was proposed to evaluate the duration (min) of formal floor sitting. After these procedures, the patients were able to sit on the floor with 155–165° of flexion for more than 30 min (Grade 3) in 20 knees, for 10–29 min (Grade 2) in seven, for less than 10 min (Grade 1) in nine and were unable to sit on the floor (Grade 0) in eight knees. Maximum knee flexion and total range of motion were 142±8.4° and 137±11° before and 152±6.6° and 151±7.4° after surgery, respectively. The American Knee Society Knee Score and Function Score were 61±17 and 46±16 before, and 97±5 (P<0.0001) and 91±13 (P<0.0001) after surgery at the final follow-up, respectively. The femoro-tibial angle in standing with one leg was 183±6° (3° of anatomical varus angulation) before and 170±3° (P<0.0001) (10° of anatomical valgus angulation) after surgery.

To investigate the effects of vibration (Vib) and hyaluronic acid (HA) on 3-dimensional cultured cartilage.Chondrocytes were obtained from metatarsophalangeal joints of freshly killed 6-month-old pigs. Twenty-four-well plates containing type I collagen sponge disks were used to culture samples. The frequency and the amplitude of the vibration of the well plate were 100 Hz and 0.5 nm, respectively. We produced 3-dimensional cartilage tissue using HA and vibration with collagen sponge as a carrier. Four different culture conditions were examined: a control HA-Vib- group, an HA-Vib+ group, an HA+Vib- group, and an HA+Vib+ group. Each group was cultured for 2 weeks. After culture days 3, 7, 10, and 14 (every 3.5 days), the levels of chondroitin 4-sulfate (C4S) and chondroitin 6-sulfate (C6S) isomers synthesized in each culture medium were measured. Histologic analysis, immunohistochemical analysis, and electron microscopic examination were performed.Mean C4S and C6S synthesis had increased rapidly after 7 days of culture and continued to increase thereafter. There were significant differences among the 4 groups (P < 0.01). Synthesis of both C4S and C6S was most abundant in the HA+Vib+ group and the lowest in the HA-Vib- group. After 1 and 2 weeks of culture, the chondrocytes had formed stratified structures on the collagen sponges in all groups, although the thickest structure was observed in the HA+Vib+ group and the thinnest in the HA-Vib- group. Under immunofluorescence, the HA+Vib+ group exhibited the strongest chromatic features. Under electron microscopy, the chondrocytes in the HA+Vib+ group exhibited many long and slender prominences on their surface, and extracellular substance could be observed associated with the cells.Our results indicate that the combination of vibration and HA activates the production of proteoglycan in 3-dimensional cultured chondrocytes and stimulates MAPK and beta-catenin. This suggests that some mechanoreceptors for vibration exist on the plasma membrane of chondrocytes and activate the intracellular signal transduction system.

To assess the relationship between bone mineral density (BMD) and varus deformity arising from bone structural changes caused by knee osteoarthritis (OA) in postmenopausal women.This cross-sectional study involved 135 consecutive postmenopausal female patients who had varus knee OA and a Kellgren-Lawrence grade > or = 2. Knee radiographs were obtained with the patient standing on one leg, and subjects were classified into 3 tertile groups according to femorotibial angle, which was taken as a measure of varus knee OA severity. We also measured the 3 subangles that make up the femorotibial angle, and focused on the varus inclination of the tibial plateau. BMD was measured in the lumbar spine, femoral neck, and medial and lateral tibial condyles using dual-energy X-ray absorptiometry. Differences between femorotibial angle tertile groups were assessed, and associations between femorotibial sub-angles and BMD values at various points were evaluated.After adjustment for age and body mass index, there was no significant association between the varus inclination of the tibial plateau and lumbar spine BMD. A weak but statistically significant negative correlation existed between varus inclination of the tibial plateau and BMD at the ipsilateral proximal femur and lateral tibial condyle.Varus inclination of the tibial plateau was significantly more severe in the femorotibial angle tertile 3 group, and in patients with lower BMD in the ipsilateral lower limb. Varus knee OA may result not only from cartilage loss but also from structural changes of the bone.

Medial closed wedge distal femoral osteotomy (MCWDFO) has been widely performed for lateral-compartment osteoarthritis since the development of a biplanar osteotomy technique using existing MCWDFO-specific plates. To further improve this system and the technique, we have developed a newly designed MCWDFO plate (TriS-MDFO; Olympus Terumo Biomaterials). The improved shape of the plate consists of a larger head–shaft angle to fit the distal femur after MCWDFO, more distally oriented distal screws to enable longer screw insertion, and a diamond-shaped plate head to avoid interference with the medial patellofemoral ligament. Technically, to overcome the difficulty in inserting proximal screws through the vastus medialis muscle, a cannulated screw system was employed. This system can prevent difficulties in removing the screw due to cross-threading when plate removal is required. Furthermore, we designed a novel compression hook device with a bulb-shaped head to hook on a screw hole to apply a compressive force to the osteotomized site. On the plate side, a characteristic 1.5 mm-thickness stopper is installed to prevent slippage of the hook device. This optimal compression system can minimize the risk of lateral hinge fracture during the compression procedure. These improvements in the TriS-MDFO may increase the ease and safety of MCWDFO.

To evaluate the outcome of a minimally invasive treatment of unstable two-part proximal humeral fractures using a J-nail.Retrospective case series.Forty-one unstable two-part proximal humeral fractures (thirty women and eleven men) with a mean age of sixty-five years (range 18 to 95 years) were studied.Closed reduction and internal fixation with J-nails.All fractures were classified using Neer's classification and were displaced and unstable. Forty of the two-part fractures were at the surgical neck and one at the anatomic neck. All patients had a closed reduction and intramedullary fixation using three J-nails. The mean follow-up period was twenty-nine months (range 2 to 4 years). Clinical assessment was performed by doctors who did not participate in the primary surgery and was graded according to Neer's scoring system.All patients experienced immediate pain relief. At the two-year follow-up, the mean angles of active forward elevation, abduction, and extension were 138 degrees (range 80 to 180 degrees), 132 degrees (range 80 to 170 degrees), and 65 degrees (range 40 to 85 degrees), respectively. According to Neer's criteria, the outcome was excellent in twenty-five patients, satisfactory in twelve, unsatisfactory in three, and a failure in one. The final Neer's score showed a significant negative correlation with age (p < 0.01).J-nail fixation has the advantage of being an almost closed method without the disadvantage of muscle transfixation associated with other methods. The procedure is simple and involves minimal invasion of the soft tissue. Shoulder and elbow function is not impeded because the nails are inserted just below the distal part of the deltoid muscle insertion. This surgical technique may be one of the more reliable and effective treatments for proximal humeral fractures.

Existing commercial finite element analysis (FEA) codes do not exhibit the performance necessary for large scale analysis on parallel computer systems. In this paper, we demonstrate the performance characteristics of a commercial parallel structural analysis code, ADVC, on Blue Gene/L (BG/L). The numerical algorithm of ADVC is described, tuned, and optimized on BG/L, and then a large scale drop impact analysis of a mobile phone is performed. The model of the mobile phone is a nearly-full assembly that includes inner structures. The size of the model we have analyzed has 47 million nodal points and 142 million DOFs. This does not seem exceptionally large, but the dynamic impact analysis of a product model, with the contact condition on the entire surface of the outer case under this size, cannot be handled by other CAE systems. Our analysis is an unprecedented attempt in the electronics industry. It took only half a day, 12.1 hours, for the analysis of about 2.4 milliseconds. The floating point operation performance obtained has been 538 GFLOPS on 4096 node of BG/L.

PurposeThe purpose of this study was to evaluate the efficacy of periarticular multimodal drug injection after medial opening-wedge high tibial osteotomy regarding the postoperative pain level.MethodsFrom January 2011 to January 2012, 70 patients underwent medial opening-wedge high tibial osteotomy. Thirty-five patients were randomly assigned to receive no injection (group I), and 35 patients were assigned to receive periarticular multimodal drug injection (group II). These 2 groups were compared regarding the postoperative pain level, frequency of additional nonsteroidal anti-inflammatory drug injections, total amount of patient-controlled analgesia, and number of times that patients pushed the patient-controlled analgesia button at each time interval. Statistical results were based on multivariate analysis of variance and repeated-measures analyses.ResultsMultivariate analysis of variance of mean visual analog scale (VAS) scores over the 2-week postoperative period showed statistical significance (P < .001). Repeated-measures analysis yielded a statistically significant difference (P = .001) for the time-by-treatment interaction, showing a clear periarticular multimodal drug injection benefit over time based on VAS scores. In addition, the mean number of times that patients pushed the patient-controlled analgesia button differed significantly between groups over time (P = .01). The VAS scores, frequency of additional nonsteroidal anti-inflammatory drug injections, mean number of times that patients pushed the patient-controlled analgesia button, and mean total amount of fentanyl consumption differed significantly within each group over time (P < .001 for all variables). However, the frequency of additional nonsteroidal anti-inflammatory drug injections and mean total amount of fentanyl consumption did not differ significantly between groups over time (P = .822, P = .529, and P = .282). Opioid- and injection-related complications were not found.ConclusionsThis prospective randomized study shows that intraoperative periarticular multimodal drug injections in patients undergoing medial opening-wedge high tibial osteotomy for unicompartmental osteoarthritis of the knee could result in significant reductions in VAS scores at 2 weeks postoperatively.Level of EvidenceLevel I, high-quality randomized controlled trial with statistically significant differences. The purpose of this study was to evaluate the efficacy of periarticular multimodal drug injection after medial opening-wedge high tibial osteotomy regarding the postoperative pain level. From January 2011 to January 2012, 70 patients underwent medial opening-wedge high tibial osteotomy. Thirty-five patients were randomly assigned to receive no injection (group I), and 35 patients were assigned to receive periarticular multimodal drug injection (group II). These 2 groups were compared regarding the postoperative pain level, frequency of additional nonsteroidal anti-inflammatory drug injections, total amount of patient-controlled analgesia, and number of times that patients pushed the patient-controlled analgesia button at each time interval. Statistical results were based on multivariate analysis of variance and repeated-measures analyses. Multivariate analysis of variance of mean visual analog scale (VAS) scores over the 2-week postoperative period showed statistical significance (P < .001). Repeated-measures analysis yielded a statistically significant difference (P = .001) for the time-by-treatment interaction, showing a clear periarticular multimodal drug injection benefit over time based on VAS scores. In addition, the mean number of times that patients pushed the patient-controlled analgesia button differed significantly between groups over time (P = .01). The VAS scores, frequency of additional nonsteroidal anti-inflammatory drug injections, mean number of times that patients pushed the patient-controlled analgesia button, and mean total amount of fentanyl consumption differed significantly within each group over time (P < .001 for all variables). However, the frequency of additional nonsteroidal anti-inflammatory drug injections and mean total amount of fentanyl consumption did not differ significantly between groups over time (P = .822, P = .529, and P = .282). Opioid- and injection-related complications were not found. This prospective randomized study shows that intraoperative periarticular multimodal drug injections in patients undergoing medial opening-wedge high tibial osteotomy for unicompartmental osteoarthritis of the knee could result in significant reductions in VAS scores at 2 weeks postoperatively.

High tibial osteotomy was performed in 73 knees of 50 patients with medial and patellofemoral compartmental osteoarthritis of the knee, which was combined with anterior advancement of the distal fragment. At the operation, parapatellar release of the retinaculum and subperiosteal elevation of contracted medial soft tissue were also adjoined. The average age of the patients at the time of surgery was 64 years. The follow-up period was an average of 58 months. On overall clinical results assessed with the Knee Society score, the average total knee score was improved from preoperative 50 points to postoperative 94, and the preoperative average functional score of 47 points increased to 92 postoperatively. At follow-up, pain from a grinding patella was not found in 68 of 73 knees and pain from grinding and deviating of the patella was relieved in more than 96% of all cases. The mean femorotibial angle was reduced from preoperative 185° to postoperative 167°. On skyline view, the width of the lateral facet joint space was widely opened postoperatively, particularly on the flexion angle of 90°. This operative procedure successfully relieved patellofemoral symptoms of the patients with medial and patellofemoral compartmental osteoarthritis of the knee.

The success rate of unicompartmental knee arthroplasty has been variable, and controversy still surrounds its use. Achieving good functional results from this surgery may require understanding surgical principles, precise operative techniques, and careful patient selection. This paper evaluates clinical results and factors influencing postoperative knee function after unicompartmental knee arthroplasty. The follow-up assessment of 109 knees that underwent unicompartmental knee arthroplasty showed that 90 of 109 knees were classified as excellent or good (82.6%) using the Hospital for Special Surgery knee scoring system. In the excellent group (54 knees), 52% of the postoperative, standing femorotibial angles converged on a range of 170 degrees to 175 degrees with a mean of 174 degrees +/- 4 degrees. The knees with residual flexion contracture after surgery showed poorer clinical results. Therefore, complete elimination of the flexion contracture during surgery is considered mandatory.

Mechanical stimulation to bones affects bone formation such as decrease of bone mass of astronauts under zero gravity, walking rehabilitation to bone fracture and fracture repair with ultrasound devices. Bone cells have been reported to sense and response to mechanical stimulation at cellular level morphologically and metabolically. In the view of mechanical vibrations, bone cells are deformed according to mechanical stimulation and their mechanical characteristics. In this study, sinusoidal inertia force was applied to cultured osteoblasts, which are a kind of bone cells, and effects of frequency and acceleration amplitude of mechanical vibration on the cells were investigated in respect of the cell proliferation, bone matrix generation and alkaline phosphatase (ALP) gene expression. The results to be obtained are as follows. The significant difference of cell density and bone mass generation between the non-vibrating and vibrating groups is found. ALP gene expression shows a peak to frequency at 50 Hz and the value of it is approximately 4.5 times as high as that of the non-vibrating group in the case of the acceleration amplitude of 0.5 G. ALP gene expression at 0.5 G is significantly larger than at 0, 0.125 or 0.25 G in the case of the frequency of 50 Hz.

Juxta-articular osteoid osteoma is a rare disorder that is difficult to correctly diagnose at an early stage. We report a case of osteoid osteoma in the calcaneus that arose near to the talocalcaneal joint. An 18-year-old female presented with symptoms of joint swelling and effusion similar to those of monoarthritis. Conservative treatment proved ineffective in achieving pain relief, and she underwent surgery 6 months later. The lesion was diagnosed by histologic examination, and it resolved after resection of the tumor.

We developed a rat model of bisphosphonate-related osteonecrosis of the jaw (BRONJ) by removing a maxillary molar tooth (M1) from ovariectomized rats after treatment with alendronate. To mimic periodontitis, some of the rats were administered Porphyromonas gingivalis (p. gingivalis) at the M1 site every 2 to 3 d for 2 wk. Rats pretreated with alendronate plus p. gingivalis showed delayed healing of socket epithelia, periosteal reaction of alveolar bone formation and lower bone mineral density in the alveolus above adjacent M2 teeth. These abnormalities were prevented by tooth socket exposure to 20 min/d low-intensity pulsed ultrasound (LIPUS), which restored diminished expression of RANKL, Bcl-2, IL-6, Hsp70, NF-κB and TNF-α messenger ribonucleic acids in remote bone marrow, suggesting LIPUS prevented development of BRONJ-like pathophysiology in rat by inducing systemic responses for regeneration, in addition to accelerating local healing. Non-invasive treatment by LIPUS, as well as low-level laser therapy, may be useful for medication-related osteonecrosis of the jaw patients.

Space radiation dosimetry measurements have been made on board the Space Shuttle STS-65 in the Second International Microgravity Laboratory (IML-2). In these measurements, three kinds of detectors were used; one is a newly developed active detector telescope called "Real-time Radiation Monitoring Device (RRMD)" utilizing silicon semi-conductor detectors and others are conventional detectors of thermoluminescence dosimeters (TLDs) and CR-39 plastic track detectors. Using the RRMD detector, the first attempt of real-time monitoring of space radiation has been achieved successfully for a continuous period of 251.3 h, giving the temporal variations of LET distribution, particle count rates, and rates of absorbed dose and dose equivalent. The RRMD results indicate that a clear enhancement of the number of trapped particles is seen at the South Atlantic Anomaly (SAA) without clear enhancement of dose equivalent, while some daily periodic enhancements of dose equivalent due to high LET particles are seen at the lower geomagnetic cutoff regions for galactic cosmic ray particles (GCRs). Therefore, the main contribution to dose equivalent is seen to be due to GCRs in this low altitude mission (300 km). Also, the dose equivalent rates obtained by TLDs and CR-39 ranged from 146.9 to 165.2 microSv/day and the average quality factors from 1.45 to 1.57 depending on the locations and directions of detectors inside the Space-lab at this highly protected orbit for space radiation with a small inclination (28.5 degrees) and a low altitude (300 km). The LET distributions obtained by two different detectors, RRMD and CR-39, are in good agreement in the region of 15-200 keV/mm and difference of these distributions in the regions of LET < 15 keV/mm and LET > 200 keV/mm can be explained by considering characteristics of CR-39 etched track formation especially for the low LET tracks.

The purpose of this research was to determine the significance of the transepicondylar line as a parameter of femoral axial alignment. Standing full-length X-ray films of 124 knees of 91 patients (63 women, 28 men) with osteoarthritis, rheumatoid arthritis, or osteonecrosis were used in this study, in which the lateral angles formed by the femoral anatomical axis intersecting with the transepicondylar line (angle a'), horizontal line (angle b'), and femoral condylar line (angle r') were measured. The mean value of angle b' in knees with neutral alignment was significantly smaller than that in knees with varus alignment, and significantly larger than that in knees with valgus alignment; no significant difference was found in angle a'. Also, there was no significant difference in angle a' among the patients with osteoarthritis, rheumatoid arthritis, and osteonecrosis. These findings suggest that the transepicondylar line, which is a stable reference of femoral rotation, is also a very reliable parameter of axial alignment of the femur. In the future design of extramedullary guiding for total knee arthroplasty, the transepicondylar line may play an important role as a parameter for proper and accurate implant setting.

<h2>Abstract</h2> Severe varus deformity in osteoarthritic knees is attributed not only to bony deformity but also to intra-articular deformity as a result of medial joint space narrowing with lateral joint space widening (increased joint line convergence angle). In such knees, correction of bony deformity by high tibial osteotomy (HTO) alone may not be capable of restoring physiological joint geometry and biomechanics. Tibial condylar valgus osteotomy (TCVO), an L-shaped osteotomy in the medial tibial condyle, has been proposed to improve articular stability and congruity by elevating the medial tibial joint line and addressing the articular component of the deformity; however, its surgical efficacy for correction of the valgus deformity is limited. Therefore a procedure combining HTO and TCVO can be a reasonable option to achieve restoration of the knee joint physiology in such situations. In our current practice, medial open-wedge distal tuberosity tibial osteotomy (MOW-DTO) has been the procedure of primary option among the HTO procedures to avoid patellofemoral overload which could be an inherent problem in medial open-wedge HTO. In this article, the surgical rationale and the combined procedure of TCVO and MOW-DTO are described.

The peptidylprolyl isomerase Pin1 is over-expressed in some human diseases including malignancies and chronic inflammatory diseases, this suggests that it contributes to the constitutive activation of certain intracellular signaling pathways that promote cell proliferation and cell invasion. Here, we investigate the possible role of Pin1 in rheumatoid arthritis (RA). Pin1 expression was immunohistochemically analyzed in synovial tissue (ST) obtained from patients with RA and osteoarthritis (OA). To investigate the correlation between Pin1 and motility and proliferation of synovial cells, Pin1 localization was immunohistochemically compared with matrix metalloproteinase (MMP)-1, MMP-3, and proliferating cell nuclear antigen (PCNA). Double immunofluorescent staining for Pin1 and p65 was performed to determine whether Pin1 is involved in nuclear factor κB (NF-κB) activation in RA-ST. Results showed Pin1 expression was significantly higher in RA-ST than in OA-ST. The expression of MMP-1, MMP-3, and PCNA was also significantly elevated in RA-ST. Double immunofluorescent staining revealed colocalization of Pin1 and p65 in the nuclei of RA-ST. These results suggest that Pin1 may be involved in the pathogenesis of RA binding with p65 to activate the proteins MMP-1, MMP-3, and PCNA. Therefore, Pin1 may play a pivotal role in the pathogenesis of RA.

本研究の目的は，緑藻類Scenedesmus quadricaudaおよび藍藻類Microcystis aeruginosaにおける優占種変遷機構解明のための基礎的知見を集積することである．高濃度リン条件下（1.55 mg/L），窒素濃度を0.1～5.0 mg/Lおよび0.5～5.0 mg/Lとした窒素制限条件にてそれぞれ単種・競合培養実験を行い，得られた各種パラメータを用い両種の優占化特性について評価した．その結果，M. aeruginosaの Δ N/ Δ Chl.a値は，窒素濃度0.5，1.0，2.5および5.0 mg/Lの条件にてS. quadricaudaより5～7倍高い値を示した．またS. quadricaudaはM. aeruginosaに比べ高い生産効率を有し，1.0～5.0 mg/Lの条件にてS. quadricaudaが，窒素濃度0.5 mg/Lの条件にてM. aeruginosaが優占化することがわかった．さらに，両種の優占種変遷の切り替わりポイントがN：P比0.3（N = 0.5 mg/L）から0.6（N = 1.0 mg/L）にかけてあることが見出された．

Space radiation dosimetry measurements have been made onboard the Space Shuttle STS-65 in the Second International Microgravity Laboratory (IML-2: 28.5 degrees x 300 km: 14.68 days) and the STS-79 in the 4th Shuttle MIR mission (S/MM#4: 51.6 degrees x 300-400km: 10.2 days). In these measurements, three kinds of detectors were used; one is a newly developed active detector telescope called "Real-time Radiation Monitoring Device (RRMD-I for IML-2 and RRMD-II with improved triggering system for S/MM#4)" utilizing silicon semi-conductor detectors and the other detectors are conventional passive detectors of thermoluminescence dosimeters (TLDs) and CR-39 plastic track detectors. The main contribution to dose equivalent for particles with LET > 5.0 keV/micrometer (IML-2) and LET > 3.5 keV/micrometer (S/MM#4) is seen to be due to galactic cosmic rays (GCRs) and the contribution of the South Atlantic Anomaly (SAA) is less than 5% (IML-2: 28.5 degrees x 300 km) and 15% (S/MM#4: 51.6 degrees x 400 km) in the above RRMD LET detection conditions. For the whole LET range (> 0.2 kev/micrometer) obtained by TLDs and CR-39 in these two typical orbits (a small inclination x low altitude and a large inclination x high altitude), absorbed dose rates range from 94 to 114 microGy/day, dose equivalent rates from 186 to 207 microSv/day and average quality factors from 1.82 to 2.00 depending on the locations and directions of detectors inside the Spacelab at the highly protected IML-2 orbit (28.5 degrees x 300 km), and also, absorbed dose rates range from 290 to 367 microGy/day, dose equivalent rates from 582 to 651 microSv/day and average quality factors from 1.78 to 2.01 depending on the dosimeter packages around the RRMD-II "Detector Unit" at the S/MM#4 orbit (5l.6 degrees x 400km). In general, it is seen that absorbed doses depend on the orbit altitude (SAA trapped particles contribution dominant) and dose equivalents on the orbit inclination (GCR contribution dominant). The LET distributions obtained by two different types of active and passive detectors, RRMDs and CR-39, are in good agreement for LET of 15 - 200 kev/micrometer and difference of these distributions in the regions of LET < 15 kev/micrometer and LET > 200 kev/micrometer can be explained by considering characteristics of CR-39 etched track formation especially for the low LET tracks and chemical etching conditions.

Mechanical stimulation to bones affects osteogenesis such as decrease of bone mass of astronauts under zero gravity, walking rehabilitation to bone fracture and fracture repair with ultrasound devices. Bone cells have been reported to sense and response to mechanical stimulation at cellular level morphologically and metabolically. In the view of mechanical vibrations, bone cells are deformed according to mechanical stimulation and their mechanical characteristics. Recently, it was reported that viscoelasticity of cells was measured using tensile and creep tests and that there was likely natural frequency and nonlinearity of cells in the sense of structural dynamics. It suggests that there is effective frequency and amplitude of mechanical stimulation on osteogenesis by bone cells. In this study, sinusoidal inertia force was applied to cultured osteoblasts, MC3T3-E1, and effects of frequency and acceleration amplitude of mechanical vibration on the cells were investigated in respect of cell proliferation, cell morphology, bone matrix generation and alkaline phosphatase (ALP) gene expression. After the cells were cultured in culture plates in a CO2 incubator for one day and adhered on the cultured plane, vibrating groups of the culture plates were set on an aluminum plate attached to a exciter and cultured under sinusoidal excitation in another incubator separated from non-vibrating groups of the culture plates. Acceleration amplitude and frequency were set to several kinds of conditions. The time evolution of cell density was obtained by counting the number of cells with a hemocytometer. The cell morphology was observed with a phase contrast microscope. Calcium salts generated by the cells were observed by being stained with alizarin red S solution and their images were captured with a CCD camera. The vibrating groups for the cell proliferation and the calcium salts staining were sinusoidally excited for 24 hours a day during 28-day cultivation. Gene expression of ALP was measured by a real-time RT-PCR method. After the vibrating groups for the PCR were excited for 6 hours, the total RNAs were extracted. After reverse transcription, real-time RT-PCR was performed. Gene expression for ALP and a housekeeping gene were determined simultaneously for each sample. Gene levels in each sample were normalized to the measured housekeeping gene levels. As a result, it is shown that saturate cell density becomes high and bone matrix generation is promoted by applying mechanical vibration and that there may be some peaks to frequency and a certain threshold value to acceleration amplitude of mechanical vibration for saturation cell density and bone matrix generation.

Contact force and contact area in the patello-femoral joint was biomechanically analyzed using seven amputated legs. The knees were fixed firmly to the experimental apparatus and 300 N of tension was applied to the quadriceps tendon. Total contact force was measured using pressure-sensitive film, and the ratio of the contact area to the patellar joint surface (%) was measured using hydrophilic vinyl polysiloxane impression material. At a Q-angle of 0° with no advancement, 10 mm and 20 mm advancement of the tibial tuberosity, the total contact force on the patello-femoral joint at a knee flexion of 45° was 266±55 N, 191±58 N and 146±58 N, respectively. The total contact force became smaller as the advancement of the tibial tuberosity changed to 5, 10, 15 and 20 mm. Especially, the total contact force with Q-angle of 0° and anterior advancement of 15 and 20 mm was significantly smaller than that with no advancement. With a Q-angle of 0°, the contact area of the patello-femoral joint at 10 mm advancement was the greatest, occupying 30.1±9.9% of the whole patellar joint surface. The mean contact pressure with Q-angle of 0° and anterior advancement of 10 mm was smaller than that with all other positions, but there was no significant difference. In this experiment, combined anterior and medial displacement of the tibial tuberosity reduced the contact force in the patello-femoral joint of the amputated legs, and an advancement of 10 mm achieved optimal reduction of force and the greatest contact area.

Bone formation is subject in vivo to mechanical stimulation. Although many researches for bone cells of osteoblastic lineage sensing and responding to mechanical stimulation have been reported mainly in the biochemical field, effects of mechanical stimulation on bone cells are not well understood. In this study, in order to clarify effects of acceleration amplitude and frequency of mechanical stimulation on MC3T3-E1, which is an osteoblast-like cell line derived from mouse calvaria, in the sense of mechanical vibrations, their cell proliferation, cell morphology, bone matrix generation and gene expression of alkaline phosphatase (ALP) were investigated when sinusoidal inertia force was applied to the cells. After the cells were cultured in culture plates in a CO2 incubator for one day and adhered on the cultured plane, vibrating groups of the culture plates were set on an aluminum plate attached to a exciter and cultured under sinusoidal excitation in another incubator separated from non-vibrating groups of the culture plates. Acceleration amplitude and frequency were set to several kinds of conditions. The time evolution of cell density was obtained by counting the number of cells with a hemocytometer. The cell morphology was observed with a phase contrast microscope. Calcium salts generated by the cells were observed by being stained with alizarin red S solution and their images were captured with a CCD camera. The vibrating groups for the cell proliferation and the calcium salts staining were sinusoidally excited for 24 hours a day during 28-day cultivation. Gene expression of ALP was measured by a real-time reverse transcription polymerase chain reaction (real-time RT-PCR) method. After the vibrating groups for the PCR were excited for 7 days, the total RNAs were extracted. After reverse transcription, real-time RT-PCR was performed. Gene expression for ALP and a housekeeping gene were determined simultaneously for each sample. ALP gene level in each sample was normalized to the measured housekeeping gene level. The results to be obtained are as follows. In the range from 12.5 to 200 Hz, saturation cell density for the cell proliferation shows tendency of increase as frequency decreases and ALP gene expression shows a peak to frequency at 50 Hz. Among 0, 0.25 and 0.5 G, saturation cell density and ALP gene expression show tendency of increase as acceleration amplitude increases.

This paper describes the effects of ultrasound stimulation on chondrocytes in three-dimensional culture in relation to the production of regenerative cartilage tissue, using collagen sponges as a carrier and supplementation with hyaluronic acid (used in the conservative treatment of osteoarthritis). It has been shown that cell proliferation and matrix production can be facilitated by considering the mechanical environment of the cultured chondrocytes and the mechanical properties of the scaffold structure used in the culture and of the stimulation used.

This paper describes the effects of the frequency and acceleration amplitude of mechanical vibration on osteoblasts, the bone cells that generate the bone matrix. Their cell proliferation and bone matrix generation were investigated when sinusoidal inertia force was applied to the cells. Bone formation is subject in vivo to mechanical stimulation. Although many researches for bone cells of osteoblastic lineage sensing and responding to mechanical stimulation have been reported mainly in the biochemical field, effects of mechanical stimulation on bone cells are not well understood. After the cells were cultured in culture plates in a CO2 incubator for one day and adhered on the cultured plane, vibrating groups of the culture plates were set on an aluminum plate attached to a exciter and cultured under sinusoidal excitation in another incubator separated from non-vibrating groups of the culture plates. Acceleration amplitude and frequency were set to several kinds of conditions. The time evolution of cell density was obtained by counting the number of cells with a hemocytometer. Calcium salts generated by the cells were observed by being stained with alizarin red S solution and their images were captured with a CCD camera. The vibrating groups for the cell proliferation and the calcium salts staining were sinusoidally excited for 24 hours a day during 28 days of culture. Gene expression of alkaline phosphatase (ALP) and runt-related gene 2 (Runx2) was measured by a real-time reverse transcription polymerase chain reaction (real-time RT-PCR) method. After the vibrating groups for the PCR were excited for 4 days, the total RNAs were extracted. After reverse transcription, real-time RT-PCR was performed. Gene expression for ALP, Runx2, and a housekeeping gene were determined simultaneously for each sample. ALP and Runx2 gene level in each sample was normalized to the measured housekeeping gene level. The following experimental results of sinusoidal excitation of osteoblasts have been shown: (a) Cell density decreased at 0.5 G with increasing frequency in the range from 12.5 to 1000 Hz and increased at 25 Hz with increasing acceleration amplitude from 0 to 0.5 G at 14 days of culture. (b) No calcium salts were observed in the non-vibrating group and the areas of calcium salts observed in the 0.5 G vibration group were larger than those in the 0.25 G group at 25 Hz at 21 days of culture. (c) The mRNA level of ALP at 0.5 G showed the peak at 50 Hz in the range from 12.5 to 1000 Hz and that at 50 Hz showed the peak at 0.5 G in the range from 0.25 to 1 G at 4 days of culture. In the case of Runx2, the same tendency was found. It has been shown that it is important to consider mechanical vibration as well as biochemical aspects in studies of the functional adaptation of cells to mechanical stimulation.

This paper describes a method to investigate the relationship between cytoskeletal deformation by mechanical stimulation and its corresponding intracellular signals for identifying mechanosensors of cells. Gene transfection of green fluorescent protein to osteoblasts enabled visualization of actin in cells. When local deformation was applied to a cell by a micropipette, the distribution of cytoskeletal actin deformation in the whole cell was automatically obtained from the two images of the cell before and after deformation by using KLT method. Calcium ion signaling response to the same mechanical stimulation was measured as the spatial and temporal changes of fluorescent intensity of fluo-4 loaded to osteoblasts. As a result, we obtained the relationship between the deformation and the biochemical signals in cells.

This paper describes effects of mechanical vibration on osteoblasts. Their cell proliferation was investigated when sinusoidal inertia force was applied to the cells. After the cells were cultured in culture plates in a CO2 incubator for one day and adhered on the cultured plane, vibration group of the culture plates was set on an aluminum plate attached to a exciter and cultured under sinusoidal excitation of 0.5 G and 12.5 Hz for 24 hours a day in another incubator separated from non-vibration group during 21 days of culture. The time evolution of cell density was obtained by counting the number of cells with a hemocytometer. The phase contrast microscopic images and the cross-sectional confocal microscopic images of cells were captured under an inverted microscope system. As a result, it is found that the mechanical vibration elongated the pseudopods of cells to enhance their mobility resulting in promoting multilayer of the cells.

This paper describes a micro device which applies cyclic strain to focal adhesions of a cell. In recent years, evidence has been growing that focal adhesions act as mechanosensors of cells which convert mechanical force into biomechanical signaling. However, there are no effective micro devices which can directly apply mechanical stimulation to each focal adhesion. Here we develop a micropillar substrate embedding micron-sized magnetic particles and enabling the micropillars to be deflected by external magnetic field. The combination of long and short micropillars produces the difference of deflection between them and enables the micropillars to apply strain to a cell. The long pillars were periodically deflected at the amplitude of approximately 1.4 μm whereas most of short pillars were not deflected. Using the magnetic micropillar substrate, we observed the deformation of an osteoblast cell at its focal adhesions. The findings indicate that the present micro device can be used for investigating mechanosensing systems of a cell.

Poster Presentations / Osteoarthritis and Cartilage 19S1 (2011) S53-S236 S129 both.Oxidatives stress was induced by pre-treatment with 250uM tertbutyl hydroperoxide (TBHP).DNA was measured with a picogreen assay, PG synthesis by sulfate incorporation, survival with the Live-Dead cell assay and cell signaling by immunoblotting with phospho-specific and control antibodies.Smad 4 translocation to the nucleus was measured by confocal microscopy.Results: With increasing donor age, chondrocytes had a reduced response (PG synthesis corrected for DNA) to IGF-1 (r = -0.63,p = 0.02), IGF-1+OP-1 (r = -0.74,p = 0.004) and a trend for OP-1 alone (r = -0.51,p = 0.08).In 21-day alginate bead cultures there was a significant reduction in DNA content with age in controls (r = -0.57,p = 0.002) and although IGF-1, OP-1, and IGF-1+OP-1 increased DNA content over controls, there was a similar age-related decline in DNA with all treatments.IGF-1 activated both the PI-3 kinase-Akt and MEK-ERK pathways while OP-1 activated Smad1,5,8 and Smad 4 translocation.DNA content in 21-day alginate beads was significantly reduced with all treatments in the presence of the PI-3 kinase inhibitor LY294002 but not with the MEK inhibitor PD98059 consistent with a requirement for Akt activation to promote chondrocyte proliferation and survival.Induction of oxidatives stress with TBHP inhibited IGF-1 activation of Akt but not ERK which was activated.Cells from older adults had significantly greater ERK activation with TBHP (p = 0.04) and greater Akt inhibition (p = 0.002) than cells from younger donors demonstrating greater susceptibility to oxidative stress (Fig. 1).TBHP did not appear to affect Smad1,5,8 phosphorylation in response to OP-1 and only modestly reduced the amount of Smad 4 translocation to the nucleus by about 20% but completely inhibited OP-1 induced PG synthesis to levels below control.Conclusions: Both increasing age and oxidative stress reduce the anabolic and survival response of normal human chondrocytes to IGF-1 and OP-1.The PI-3kinase-Akt pathway is required for survival and proliferation of chondrocytes in response to both IGF-1 and OP-1 even though only IGF-1 directly activates this pathway.Although oxidative stress inhibited OP-1 stimulation of PG synthesis it did not appear to significantly inhibit Smad signaling suggesting other pathways are involved.In previous work we have shown OP-1 promotes IGF-1 signaling by increasing IGF receptor expression and so the effects of oxidative stress on the response to OP-1 may be due to inhibition of the IGF-1 signaling rather than directly inhibiting OP-1 pathways.

Cell therapy is expected to a new tool to treat refractory diseases. In heart regeneration, it has been firstly conducted with needle injection of cell suspensions. Recently, cell sheet engineering emerged as another method of cell therapy. Cell sheet is prepared with a temperature responsive dish by temperature reduction. It is a thin-patch-like tissue construct and its thickness is several tens of micrometers. It is composed of cells and intrinsic extra cellular matrix only. The transplantation of the cell sheet has been already conducted in animal experiments and even in clinical trials. The cell sheet is transplanted at the surface of the heart, but it is difficult to transplant the cell sheet under the beating heart. To overcome this difficulty, we designed a device that was composed of two thin polymer films that have different friction. The films were made of polyurethane, polyethylene, or polypropylene. The cell sheet was set up on the device by sandwiching it with the less frictional film and the more frictional film. In this paper, using two different films having the different friction, the cell sheet was successfully transplanted to the static round polymer surface, the harvested heart, and even the beating heart of pig by removing the films step by step using the difference in friction. Also, surface properties such as friction, adhesion force and roughness of the films were studied by an atomic force microscopy (AFM). From the results of the study, the friction of the film was found to be likely proportional to the adhesion force and the inverse of roughness.

Purpose: We performed clinical and radiographic evaluation of patients with medial compartmental osteoarthritis of the knee who had undergone treatment with new hemi-open closed wedge high tibial osteotomy (hybrid HTO) followed by early full weight bearing. This surgical procedures is adopted for sever varus knee, young patients, medial compartmental osteoarthritis (OA) accompanied with patello-femoral OA. Hybrid HTO procedures are demonstrated and clinical results and radiographic analysis were performed. Methods: Hybrid HTO was performed in 18 knees of 14 patients of an average age of 62 years (range 54-69) at the time of the operation. All patients were diagnosed as primary OA knees. We established an early ROM exercise and permitted partial weight bearing one week and full weight bearing walk two weeks after their osteotomy. The average follow-up period was 16 months (range 12 to 48 months). Clinical examinations of the knee joints in our patient cohort consisted of both subjective and objective parameters that were recorded and documented using the Japan Orthopaedic Association OA Knee Scoring System (JOA score) and Oxford score. These evaluations were carried out pre-surgically and at the time of follow-up. Additional clinical findings that were assessed included range of motion, and possible post-surgical complications. Radiological evaluations were carried out on the femoro-tibial angle (FTA), using an AP weight bearing radiograph of a single leg, with the knee joint in extension. A weight bearing line (WBL) ratio was calculated using standing long-cassette radiographs of the lower extremities. Results: The JOA Score and Oxford score showed significant improvement from 62±5.3, 38±10 points to 90±5.3, 16±3.5 points, respectively. Extension of the knee improved from -9.6±7.5° to -0.7±2.7°, and flexion changed from 130±11° to 128±8.7°. Prior to surgery, the average femoro-tibial angle during standing was 188±3.3° (8° anatomical varus) but measured 169±2.1° (11° valgus) at the time of follow-up. There were no instances of non-union or implant failure in any of our patient subjects. Their average WBL ratio was -7.5±15.5%, indicating that the WBL had shifted toward the medial compartment. After surgery, the the WBL ratio shifted to 71±8.5%, indicating that the WBL had moved toward the lateral compartment of the knee. Conclusions: We contrived new operation procedure of closed wedge HTO and obtained good results clinically and radiographicaly. All patients could full weight bearing walk at two weeks after surgery. This procedure is adapted for patients who are relatively young and have high activity. Overall, this procedure can make shortening of the length of a leg the minimum. Hybrid HTO is a highly successfully course of treatment for correcting sever knee malalignment in patients with medial compartmental OA of the knee. View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Mechanical stimulation to bones affects bone formation such as decrease of bone mass of astronauts under zero gravity, walking rehabilitation to bone fracture, and fracture repair with ultrasound devices. Bone cells have been reported to sense and response to mechanical stimulation at cellular level morphologically and metabolically. In the view of mechanical vibrations, bone cells are deformed according to mechanical stimulation and their mechanical characteristics. In this study, sinusoidal inertia force was applied to cultured osteoblasts, which are a type of bone cells, and effects of mechanical vibration duration at 0.5 G and 25 Hz on the cells were investigated in respect of the cell proliferation and alkaline phosphatase (ALP) gene expression. The results to be obtained are as follows. With respect to the cell proliferation, cell saturation density monotonically increased with mechanical vibration duration. With respect to ALP gene expression, bone generation was significantly promoted at the 12 h/day vibration group.

This paper describes a micro device which applies cyclic strain to focal adhesions of a cell. In recent years, evidence has been growing that focal adhesions act as mechanosensors of cells which convert mechanical force into biomechanical signaling. However, there are no effective micro devices which can directly apply mechanical stimulation to each focal adhesion. Here we develop a micropillar substrate embedding micron-sized magnetic particles and enabling the micropillars to be deflected by external magnetic field. The top of the micropillars were coated with a fibronectin, a kind of protein which promotes the adhesion of cells. Moreover, we stained this protein to check the condition of the coating and to detect the position of pillars. Using the magnetic micropillar substrate, we observed the deformation of an osteoblast cell at its focal adhesions. The findings indicate that the present micro device can be used to investigate mechanosensing systems of a cell.

According to previous studies, when some mechanical vibration is operated to osteoblast-like MC3T3-E1 cell, proliferation of the cell depends on the frequency and acceleration amplitude of applied vibration. But there are lots of unsolved mechanism between biomechanical stimulation and cellular behavior. In this study, the attention was focused to the effects of mechanical vibrating term on cultured osteoblasts. Cells, MC3T3-E1, were seeded in three culture plates. After seeding, the three plates were left still in a CO_2 incubator. And two plates were excited by electromagnetic exciter at frequency of 12.5Hz and acceleration amplitude of 0.5G in the incubator. Non-stop vibration was applied to one of two plates, which was called "group 1". A regular-term vibration was given to another plate, called "group 2". One plate was set still without vibration, called "control group". Cell density was measured and the medium in plates was changed every 3days. The difference between control group and vibration group was investigated by the growth curve.

This paper describes a method to investigate the relationship between cytoskeletal deformation by mechanical stimulation and its corresponding intracellular signals for identifying mechanosensors of cells. Gene transfection of green fluorescent protein to osteoblasts enabled visualization of actin in cells. When local shear deformation was applied to a cell by a micropipette, the distribution of cytoskeletal actin deformation in the whole cell was automatically obtained from the two images of the cell before and after deformation by using KLT method. Calcium ion signaling response to the same mechanical stimulation was measured as the spatial and temporal changes of fluorescent intensity of fluo-4 loaded to osteoblasts.

This paper described development of a micro device which applies mechanical vibration stimulation to focal adhesions of a cell. In recent years, evidence has been growing that focal adhesions act as mechanosensors of cells which convert mechanical force into biomechanical signaling. However, there are no effective micro devices which can directly apply mechanical stimulation to each focal adhesion. Here we develop a micropillar substrate embedding micron-sized magnetic particles and enabling the micropillars to be deflected by external magnetic field. The combination of long and short micropillars produces the difference of deflection between them and enables the micropillars to apply deformation to cells. The long pillars were periodically deflected at the amplitude of approximately 1.4 μm whereas many of short pillars were not deflected. The cell culture on the magnetic micropillar substrate revealed that this device can apply periodic deformation to focal adhesions of a cell. These findings indicate that the present micro device can be used for investigating mechanosensing systems of a cell.

カルシウムおよびエチレンジアミン四酢酸 （EDTA）制限条件下における培養実験により藍藻類Microcystis aeruginosa （M. aeruginosa）の増殖に及ぼすカルシウムおよびEDTA濃度の影響について検討した。M. aeruginosaのカルシウムの要求量を測定するために，カルシウムおよびEDTA濃度がそれぞれ25および13 μmol/lで吸収実験を行った。吸収実験の結果は，M. aeruginosaの細胞密度が5.0×106 cells/mlにまで達したが，M. aeruginosaの吸収によるカルシウム濃度の減少は見られなかったことを示した。M. aeruginosaのカルシウムの要求量は窒素やリンのような栄養塩と比べて非常に少ないことを示唆している。カルシウムおよびEDTA濃度をそれぞれ0から25 μmol/lおよび0から13 μmol/lと変えて培養実験を行うことにより，M. aeruginosaの増殖に及ぼすカルシウムおよびEDTAの影響について検討した。EDTAを加えていない培地において，カルシウム濃度が2.5 μmol/l以上のときはM. aeruginosaの細胞密度は1.5×107 cells/mlにまで達したが，カルシウム濃度が0 μmol/lのときには細胞密度が9.0×103 cells/mlとM. aeruginosaの増殖が抑制された。カルシウム濃度2.5 μmol/l，EDTA濃度1.3 μmol/l以下のときはM. aeruginosaはよく増殖したが，EDTA濃度を13 μmol/lに上げると抑制された。これは，EDTAのモル量がカルシウムよりも多いときM. aeruginosaの増殖が抑制されることを意味している。培養実験の結果はM. aeruginosaの増殖にはカルシウムが不可欠であり，EDTAと錯体を形成することにより培地中に無機態のカルシウムが存在しなくなるときに増殖が強く抑制されることを示唆している。

Bone cells are adaptive to surrounding mechanical conditions. Osteoblasts, one of bone cells, have been reported to be sensible to mechanical stimulation and change the generated bone mass. Activation of the signaling molecules in relation to the initial mechanoreception appears to be mediated though changes in the cytoskeleton. In this study, we propose a method to visualize cytoskeletal actin fibers in a living osteoblast under applied shear deformation and measure the local deformation of actin fibers. Transfection of MC3T3-E1, which is an osteoblast-like cell line, with GFP-actin was performed using a transfection reagent. Shear deformation was applied to the cell using a micropipette. As a result of the experiment, it is shown to be able to recognize the specific points such as points crossed by the actin fibers and obtain the local deformation vectors of the actin fiber network at the specific points in the cell. The present method contributes to not only obtaining the deformation distribution of actin fibers in cells but also understanding the mechanotransduction mechanisms.

Purpose: Intra-articular injections in the knee joint are commonly used for therapeutic and diagnostic goals concerning knee pathology. Several approaches are used to establish an intra-articular injection in the knee joint, however accuracy rates differ per approach. The primary objective was to summarize the evidence concerning the accuracy of different approaches for intra-articular injections in the knee. Methods: The literature was systemically reviewed in online databases Pubmed and Embase until June 2009. Two reviewers (JH, MR) independently applied the inclusion and exclusion criteria and inclusion was reached by consensus. Risk of bias of the included studies was assessed independently by 2 reviewers using the QUADAS-tool. Study characteristics, accuracy data, other outcome measures, results and conclusions were independently extracted by 2 reviewers. A trained statistician pooled the accuracy rates per used injection approach. Results: In total, 9 studies were included. The superolateral approach with the knee in extension was studied most (230 injections) and resulted in the highest pooled accuracy of 89% (95% C.I. 85%-93%). Pooling of the medial midpatellar approach, the anterolateral approach and the anteromedial approach resulted in the lowest pooled accuracy rates, respectively in 56% (95% C.I. 46%-68%), 70% (95% C.I. 64%-77%) and 71% (95% C.I. 65%-78%). Conclusion: Based on the results of this systematic review the authors recommend the superolateral approach with the knee in extension for the intra-articular injection of the knee joint.

In the previous study, the mechanical stress affects the proliferation of osteoblast-like MC3T3-El cell. The mechanism of the stress-induced cell proliferation remains unclear. In this study, we examined the involvement of mitogen-activated protein kinase (MAPK) and Akt pathway in the mechanical vibration and observed the alteration of cellular morphology under microscope. On 11 day, the mechanical vibration decreased the expression level of Akt and significantly increased the expression level of phospho-Akt. The area of the osteoblast in the vibration group was larger than the non-vibration group.

Liposomal bupivacaine has a paucity of data regarding narcotic requirements and hospital length of stay in comparison to other peri-articular injections, specifically in the total hip arthroplasty (THA) population.69 patients who underwent THA by a single surgeon were divided into two cohorts over a 3 year period in this retrospective study comparing narcotic requirements, hospital length of stay and cost. The study group (n = 29) received liposomal bupivacaine whereas a matched control group (n = 40) received a pharmacy-mixed cocktail in peri-articular structures. Statistical and clinical differences were reported in this unfunded study.No difference was found in hospital length of stay [2.9 days in the study group (range 1–14) versus 3.1 days (range 1–11) in the control group, p = 0.101], however, the study group required less narcotics per day [22.6 mg (range 5–53.3) versus 29 mg (range 6.7–80.8) in the control group, p = 0.045]. The clinical difference between cohorts averaged less than one pill per day of hospitalization. The cost per patient of the local injection was more than 11 times greater in the liposomal bupivacaine group.Liposomal bupivacaine demonstrated a statistical improvement in narcotic requirements but not in hospital length of stay in comparison to a control group. The effects of liposomal bupivacaine on narcotic requirements and hospital length of stay may not justify its use in total hip arthroplasty patients given the substantial cost of these injections and the minimal clinical difference in outcomes compared to a more cost-effective injection.

Deformation of actin fibers in a living osteoblast under applied shear deformation has been visualized by green fluorescent protein transfection. We obtained displacement of each position of actin fibers by a manual method and KLT method. Comparing two results, we confirmed that KLT method is able to obtain deformation of actin fibers in a cell. Actin fibers were moved in the direction of the tension of actin fibers when a part of actin fibers is broken. This result indicates that static equilibrium with actin fiber's tension play an important role in mechanical structure of a cell.

Bone cells are adaptive to surrounding mechanical conditions. Osteoblasts, one of bone cells, have been reported to be sensible to mechanical stimulation and change the generated bone mass. Viscoelastic properties of such cells are predicted to be related to this phenomenon in the view of mechanical dynamics. In order to find the effective stimulation on the bone formation, it is necessary to understand the viscoelastic properties of the cells. Especially in the case of bone cells, it is important to consider their adhesive condition because they attach on surfaces of bone matrices. In this study, we measured dynamic viscoelastic properties of a cultured osteoblast, MC3T3-E1, under adhesive condition. Using the experimental results, we derived a model for viscoelasticity of the cell and identified the value of each element in this model. The cells were seeded on a glass plate in a petri dish. After the cells were cultured for one day and adhered on the glass plate, it was vertically raised and fixed on a piezo actuator. The center of the cell surface was aspirated with an L-shaped micropipette to be held. The glass plate was moved with the piezo actuator. The load applied to the cell was obtained by measuring the deflection of the micropipette whose spring constant was calibrated after each test. Deflection of the micropipette and elongation of the cell were measured by captured image during the test. As a result, the dynamic viscoelasticity of the cells was measured and modeled, and the value of each element in this model was identified.

This paper describes the effects of vibration stimulation on chondrocytes in three-dimensional culture in relation to the production of regenerative cartilage tissue, using collagen artificial skin as a carrier and supplementation with hyaluronic acid (used in the conservative treatment of osteoarthritis), and the mechanism of the adaptive response of chondrocytes to mechanical loading. The experimental condition imitates an environment of articular cartilage in vivo that chondrocytes are completely surrounded by the extracellular matrix and receives mechanical stimulation for the weight-bearing mechanics. Chondrocytes were isolated from articular cartilage of porcine metatarsophalangeal joints. Experiments were performed under four different culture conditions: control condition, in which chondrocytes were cultured with atelocollagen gel and collagen artificial skins, and no vibration (HA−Vib−); HA−Vib+, in which chondrocytes were cultured in atelocollagen gel and collagen artificial skins with vibration treatment for 2 weeks; HA+Vib−, in which chondrocytes were cultured in medium containing 0.1% hyaluronic acid; and HA+Vib+, in which chondrocytes were cultured in medium containing 0.1% hyaluronic acid with vibration treatment for 2 weeks. Histologic analysis was conducted at 14 days of culture. The proliferation of chondrocytes was obtained by counting the number of cells with a hemocytometer after 3, 7, 10, and 14 days of culture. The expression of Sox 9 and β-catenin was detected by western blotting analysis. Sox 9 has been reported of involvement in transcription of type IX collagen that binds cartilage-specific type II collagen fibrils. β-catenin plays an important role of signaling pathways of cell proliferation although the relationship between β-catenin and mechanical vibration stimulation has not been clarified yet. The obtained results are as follows. The mechanical vibration enhanced the thickness of extracellular matrix of chondrocytes in histologic section at 14 days of culture and increased the expression of Sox 9. In addition, the mechanical vibration significantly increased the number of chondrocytes after 10 days of culture and promoted the expression of β-catenin. These results show that mechanical vibration promotes the matrix production and proliferation of chondrocytes and that a part of important signaling pathways in relation to mechanical vibration stimulation and proliferation of chondrocytes has been revealed.

This paper describes effects of mechanical vibration on osteoblasts. Their bone mass generation was investigated when sinusoidal inertia force was applied to the cells. After the cells were cultured in culture plates in a CO2 incubator for one day and adhered on the cultured plane, vibration group of the culture plate was set on an aluminum plate attached to a exciter and cultured under sinusoidal excitation of 0.5 G and 25 Hz for 24 hours a day in another incubator separated from non-vibration group during 28 days of culture. Gene expression of alkaline phosphatase (ALP) was measured by a real-time reverse transcription polymerase chain reaction method. ALP activity was measured by Azo-dye method. Calcium salts generated by the cells were observed by being stained with alizarin red S solution. As a result, it is found that the mechanical vibration accelerates the gene expression and protein generation of ALP, and the calcium salt generation.

The healing of articular cartilage that possesses little capacity for self-repair after having been damaged is still a clinical problem. This paper describes the effects of vibration stimulation on chondrocytes in three-dimensional culture that imitates actual articular cartilage in relation to the production of regenerative cartilage tissue, using collagen gel and artificial skin as a carrier. The obtained results are that the mechanical vibration advances the matrix production and the proliferation of chondrocytes.

The use of artificial bone graft substitutes has increased as the surgical application for large bone defect. Beta-tri calcium phosphate (β-TCP) is the only bone substitute which is replaced and absorbed to the bone. In the present study we investigated whether low-intensity pulsed ultrasound (LIPUS) accelerates bone ingrowth into the pores of β-TCP carried with bone marrow. Thirty six rats were used and these rats were divided into 4 groups, control group, β-TCP with LIPUS group, β-TCP carried with bone marrow and β-TCP carried with bone marrow and LIPUS. Specimens were harvested on 2, 4 and 6 weeks after implantation, and were analyzed by HE and TRAP staining. The new bone formation in the β-TCP carried with bone marrow and LIPUS was significantly larger than that of similarly implanted P-TCP that was not exposed to LIPUS. The new bone formation in the P-TCP without bone marrow was not observed. LIPUS application does not significantly increase the activity of osteoclast in comparison with similarly implanted β-TCP that was not exposed to LIPUS.

The healing of articular cartilage that possesses little capacity for self-repair after having been damaged is still a clinical problem. This paper describes the effects of vibration stimulation on chondrocytes in three-dimensional culture that imitates actual articular cartilage in relation to the production of regenerative cartilage tissue, using collagen gel and artificial skin as a carrier. The obtained results are the mechanical vibration advances the matrix production and proliferation of chondrocytes.

To evaluate clinical outcomes between hybrid closed wedge high tibial osteotomy (HCWHTO) and total knee arthroplasty (TKA) for advanced medial compartmental osteoarthritis of the knee (advanced knee OA).In more than grade 3 OA based on the Kellgren-Lawrence classification, when patients' age was less than 60 years or activity level was more than level 5 based on the UCLA activity score, 22 knees (18 patients) underwent HCWHTO. The other 22 knees (18 patients) that underwent TKA were evaluated retrospectively. Muscle strength was evaluated preoperatively and at 1 year postoperatively. The visual analogue scale (VAS) and Japanese version of the Knee injury and Osteoarthritis Outcome Score (J-KOOS) were used to evaluate clinical outcomes preoperatively and at a mean 66-months follow-up.All postoperative muscle strength measures improved to preoperative equivalent levels in the HCWHTO group; they were significantly higher in the HCWHTO group than in the TKA group (p < .05). The VAS score and total J-KOOS significantly improved in both groups (HCWHTO, p = .001; TKA, p = .040); there were no significant differences in the scores between the groups at the final follow-up. Hybrid closed wedge HTO significantly improved the activities of daily living and sport/recreation scores, whereas TKA did not at the final follow-up.In advanced knee OA, HCWHTO led to improved muscle strength, and its midterm clinical outcomes were equivalent to those of TKA. To postpone or even to avoid TKA, HCWHTO is considered an appropriate treatment for young and high-activity patients with advanced knee OA.Therapeutic Level III.

Bone cells are adaptive to surrounding mechanical conditions. Osteoblasts, one of bone cells, have been reported to be sensible to mechanical stimulation and change the generated bone mass. Viscoelastic properties of such cells are predicted to be related to this phenomenon in the view of mechanical dynamics. In order to find the effective stimulation on the bone formation, it is necessary to understand the viscoelastic properties of the cells. Especially in the case of bone cells, it is important to consider their adhesive condition because they attach on surfaces of bone matrices. In this study, we measured tensile, static and dynamic viscoelastic properties of a cultured osteoblast, MC3T3-E1, under adhesive condition. Using these experimental results, we derived a model for viscoelasticity of the cell and identified the value of each element in this model. The cells were seeded on a glass plate in a petri dish. After the cells were cultured for one day and adhered on the glass plate, it was vertically raised and fixed on a piezo actuator. The center of the cell surface was aspirated with an L-shaped micropipette to be held. The glass plate was moved with manual, an electric motor or the piezo actuator according to the types of tests. The load applied to the cell was obtained by measuring the deflection of the micropipette whose spring constant was calibrated after each test. Deflection of the micropipette and elongation of the cell were measured by captured image during the test. As a result, the viscoelasticity of the cells was measured and modeled, and the value of each element in this model was identified.

This paper describes the effects of ultrasound stimulation and hyaluronic acid on chondrocytes in three-dimensional culture. Type I collagen sponge was used for a scaffold of chondrocytes as well as 0.2 % type I collagen gel. As a result of the experiments, it is shown that there is the significant difference in cell density between the groups with and without the ultrasound stimulation and in amount of chondroitin 4 and 6 sulfates between the groups with and without both the ultrasound and hyaluronic acid after 14 days of culture.

Cells response to mechanical stimulation. It is known that mechanical stimulation affects bone formation in ultrasound therapy. It is considered that a cell is a mechanical system which has sensors,controllers and actuators.In this study,we investigated effects of amplitude and frequency of mechanical vibration on cell proliferation,bone mass generation and ALP gene expression by in-vitro cell culture. It is shown that mechanical vibration affects them according to amplitude and frequency.

Objective: It is essential to have sufficient numbers of cells for bone regeneration. We previously reported that LIPUS exposure to rodent fractured femurs or sockets of extracted teeth recruited cells from sites remote to the lesion through peripheral blood vessels (Kumagai, Takeuchi et al, J Orthop Res 2012 and Hidaka et al, Int J Anal Bio-Sci 2015). In the present study, we tried to show LIPUS exerted its anabolic action systemically on tricalcium phosphate (β-TCP) discs implanted in the back of rats, which were not directly treated with LIPUS. Materials and Methods: Four pairs of male Sprague Dawley rats were operated on as previously described. A week later, 3 β-TCP discs were implanted in the dorsal aspect of sham operated control rats and the experimental rats. On and following the day of implantation, the 2 discs closer to the rat head only in one of the pair were exposed to LIPUS every 24 hours for 2 weeks as described. Results and Discussion: Except in one rat, which showed enlarged spleen and adrenal body, no abnormality was found. Body weight, histology, and transfer of injected fluorescence-conjugated protein from one to the other rat suggested the operation was successful. In the β-TCP discs of LIPUS-untreated side rats, we observed invaded cells and blood vessels present in numbers between those of the LIPUS-exposed and the control rats. Real-time PCR and immunohistochemistry analysis also showed consistent results. Given these findings, the systemic effect of LIPUS may be more influential than we used to assume.