Gadd45beta is known to be associated with cell growth control, apoptosis, and the cellular response to DNA damage. This gene is known to be mechanosensitive in chondrocytes under hydrostatic pressure. However, the expression and function in articular cartilage is not well understood. Here we review our recent findings on Gadd45beta expression and function in osteoarthritic cartilage. Gadd45beta was expressed at higher levels in cartilage from normal donors and patients with early osteoarthritis (OA) than in cartilage from patients with late-stage OA. In early OA, Gadd45beta was distributed variably in chondrocyte clusters, in middle and deep zone cells and in osteophytes. Gadd45beta down-regulated COL2A1 mRNA and promoter activity. Nf-κB overexpression increased Gadd45beta promoter activity, and siRNA Gadd45beta decreased cell survival per se and enhanced tumor necrosis factor α-induced cell death. Gadd45beta stimulated MMP-13 promoter activity through the JNK-mediated phosphorylation of JunD, partnered with fra2, in synergy with Runx 2. Gadd45beta enhanced Col10A1 transcription via the MTK1/MKK3/6/p38 axis and the activation of C/EBPβ-TAD4 in terminally differentiating chondrocytes. These findings suggest that Gadd45beta may play an important role in regulating chondrocyte homeostasis by modulating the collagen gene and promoting cell survival in normal cartilage and in early OA.

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The mainstay of rheumatoid arthritis (RA) treatment is the application of disease-modifying antirheumatic drugs (DMARDs). New and highly effective DMARDs have continued to emerge particularly in recent years that include biologic agents, which target tumor necrosis factor (TNF), interleukin-6 (IL-6) receptor and T-cell costimulation. Furthermore, treatment strategies have changed in order to perform early intervention and to maintain tight disease control thereafter. While clinical and observational trials on drugs and strategies have been highly enlightening, rheumatologists are currently overwhelmed by this information, which does not always allow one to decide on the best treatment strategy. The management of RA with biologic agents may also differ among rheumatologists. In this paper, several aspects of biologic agents are evaluated using the data of current literature, and strategic algorithms for RA are also described.

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Background: Since 2005 we have performed cylindrical costal osteochondral autograft for reconstruction of large defects of the elbow due to osteochondritis dissecans.
Methods: Thirty-seven male patients were followed for 18 months with elbow pain due to advanced osteochondritis dissecans whose elbows showed full-thickness articular lesions ≥ 15 mm in diameter. Clinical, radiographic and magnetic resonance imaging (MRI) outcomes were evaluated at a mean follow-up of 38 months (range, 18-60 months).
Results: All cases showed rapid functional improvement after costal osteochondral autograft and they returned to their former activities, including sports. Seven minor surgeries were added, including screw removal, free body removal and shaving of protruded cartilage. Mean elbow function as assessed using the clinical rating system of Timmerman and Andrews was 114 preoperatively, improving to 176 at follow-up, and to 187 after the seven additional operations. Bony union of the graft radiologically was obtained within 3 months in all cases. Revascularization of the graft depicted on T1-weighted MRI imaging and congruity of the reconstructed articular surface depicted on T2-weighted MRI or short tau inversion recovery (STIR) imaging were assessed at approximately 12 and 24 months postoperatively. Functional recovery was good and all patients were satisfied with the final outcomes.
Conclusion: Cylindrical costal osteochondral autografting was useful for treatment of severely damaged elbows such as an articular defects caused by osteochondritis dissecans. Functional recovery was rapid postoperatively. Additional operations were performed for 7 of the 37 cases, while the remaining cases showed almost full recovery. All patients were satisfied with the results, although long-term follow-up is required.

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It is difficult to place cementless acetabular components, as performed in Europe and America, because the majority of cases of osteoarthritis (OA) of the hip in Japan are caused by acetabular dysplasia.
The characteristics of Japanese OA of the hip are discussed as follows;
1: There is often a superoanterior acetabular bony defect due to acetabular dysplasia.
2: It is difficult to insert the cementless acetabular components into the small and shallow acetabulum.
3: It is difficult to find the true anatomical position of the acetabulum because of curtain osteophytes producing a ‘double floor’ of the acetabulum
4: The press-fit technique for fixation of the acetabular components is not effective in some cases. Therefore, screw fixation is necessary for certain primary fixation.
5: Excessive anteversion of the femoral neck exists in some cases.
6: Some cases have large marginal osteophytes around the acetabulum.
The problems these characteristics can induce are discussed as follows;
1: Bony containment is insufficient if the cementless acetabular component is placed at the anatomical position of the acetabulum.
2: The placement of the cementless acetabular components tends to be in the lateral position.
3: If large artificial femoral heads are becoming larger, then the thickness of the polyethylene liners are becoming thinner.
4: With screw fixation there is a risk of injuring blood vessels.
5: Bony or soft tissue impingement might cause some limitation to the range of motion or it may increase the risk of dislocation.
In this paper we will be explaining tips, tricks, and pitfalls to help ensure a successful placement of the cementless acetabular components based on the above.

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Background: It is still controversial to resurface the patella during total knee arthroplasty (TKA). In this study, we focused on the configuration of the femoral component and the shape of the patella.
Methods: Four different trial femoral components were inserted into a saw-bone of the femur. In each femur, a K wire of 2.0 mm in diameter was inserted through the medial and lateral epicondyles. The saw-bone was attached to a specially designed measuring device so that the femur could be rotated around the K wire. The femur was rotated to express flexion of the knee in 15° increments up to 130° of flexion. A picture of the femoral condyle was taken in each angle of flexion. On each image, the contour of the component was drawn and the configuration of the patellar groove was compared among the systems.
Results: The results showed that the patellar groove of the Zimmer LPS has a wide and deep shape, and the Stryker NRG has the almost the same configuration of the patellar groove with the normal knee. The differences of the patellar groove configuration would induce different clinical results after TKA regardless of the resurfacing of the patella. The shape of the patella is one factor for resurfacing. The patellar groove of Stryker NRG matches the shape of the normal femur. Therefore, the patella with an abnormal shape should be resurfaced even though the cartilage is intact.
Conclusion: Resurfacing of the patella should be decided according to several conditions such as patellar cartilage damage, the shape of the patella and the configuration of the femoral component used in TKA.

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Objective: The aim of this study was to characterize the histological and immunohistochemical properties of the synovial tissue and the biological properties of cultured synovial cells of rheumatoid arthritis (RA) patients undergoing treatment with biologics.
Methods: Samples of synovial tissue were taken from 15 RA patients who underwent surgery of the knee joint (8), hip joint (5), and ankle joint (2). Biologics were administered to these patients (infliximab, n=7; etanercept, n=5; tocilizumab, n=3); five RA patients who were given no such agents were used as the control group. The histopathological findings were evaluated using the histological scoring system reported by Rooney, and the relationship between the histological findings and the clinical features evaluated using the disease activity score (DAS) 28-ESR were investigated. The cultured synovial cells from the surgical specimen were analyzed for the expression levels of cytokines, chemokines, and growth factors by using the suspension array system. We also examined the immunohistochemical localization of each factor.
Results: Total Rooney's inflammation scores were significantly different in the biologics and non-biologics groups, and also in the scores for synoviocyte hyperplasia, blood vessel proliferation, perivascular infiltrates of lymphocytes, and focal aggregates of lymphocytes. Clinically, patients with high DAS28-ESR scores also had high scores in Rooney's evaluation. In cultured synovial tissue, suspension array evaluation showed that the expression of interleukin-6 (IL-6), IL-8, IL-9, IL-15, IL-17, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha were significant. Immunohistochemical examination revealed that these cytokines or growth factors were positive in the macrophages or lymphocytes beside the blood vessels.
Conclusion: We believe that treatment with biologics mediated the reduction of synovial tissue, especially the reduction in synovial cell proliferation in the lining layer, and the reduction of lymphocyte infiltration around the blood vessel formations by suppressing the expression of cytokines or growth factors.

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Objective: In this study, we reviewed and compared our surgical results of implant arthroplasty (IA) and trapeziometacarpal arthrodesis (AD).
Methods: A retrospective review was undertaken of IA and AD cases, that were performed between 2000 and 2007. There were 10 cases who were actively followed up for over 5 years in our hospital. Pre- and postoperative clinical and radiographic data were reviewed. The average age of the IA group was 70.5 years and that of the AD group was 65.5 years. The average follow-up term was 94.9 months for the IA group and 88.8 months for the AD group. According to Eaton's radiographic evaluation, there were 3 grade II cases, 6 grade III cases, and 1 grade IV case in the IA group. There were 5 grade II and grade III cases respectively in the AD group. All IA group patients underwent joint replacement with Avanta (Small Bone Innovations, USA), and among the AD group, fixation with tension band wiring was used for 5 cases and screws (Acutrak, Kobayashi Medical, Japan) for the remaining 5 cases. The items evaluated included Eaton's clinical criteria (without joint instability), radiographic changes, key pinch and complications.
Results: No statistically significant differences between the two groups were found for key pinch improvement and Eaton's clinical criteria. In the IA group, there was no scaphotrapeziotrapezoid (STT) or metacarpophalangeal (MP) joint arthritis. However, there were 2 cases of loosening or sinking of the implant and such patients had occasional pain. In the AD group, radiographic progression of STT joint arthritis occurred in 3 patient thumbs, but only 1 patient was symptomatic. There were no cases of MP joint arthritis. There were 2 nonunions and one patient complained of pain.
Conclusions: For most patients, implant arthroplasty or arthrodesis reduced pain and improved function. Although implant loosening or sinking was identified in some cases in the IA group, there was no development of STT or MP joint arthritis and all patients maintained adequate range of motion of the thumb. IA appeared to be a better method than AD for individually selected patients.

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Objective: The treatment strategy for osteochondritis dissecans of the knee depends on various factors such as patient activity, open or closed growth plates, radiographically determined arthroscopic stage, and location, size, and stability of osteochondral lesions. In our hospital, we adopt conservative therapy for patients with stable osteochondral lesions and surgical therapy for patients with unstable lesions or lesions that do not heal after conservative therapy. The surgical procedure is selected depending on the following factors: open or closed growth plates, arthroscopic stage, location, size, and amount of bony osteochondral lesions.
Methods: We examined the clinical outcome in 39 patients (43 knees) with osteochondritis dissecans of the knee treated at our hospital from 2003 to 2012. Thirteen patients (17 knees) were treated using conservative therapy and 26 (26 knees) using surgical therapy, respectively. Of the 26 surgical patients, 5 were treated using the arthroscopic microfracture method, 14 using internal fixation with bioabsorbable pins or bone strips from the tibia, 1 using mosaicplasty, and 6 using autologous chondrocyte implantation with platelet-rich plasma gel. The clinical outcomes in all patients were evaluated according to the Hughston criteria and Lysholm score.
Result: The clinical outcomes were satisfactory in all patients (good in 20 patients and excellent in 18 patients) according to the Hughston criteria, and the average Lysholm score was high (97.2 points).
Conclusion: The selection of the surgical procedure in patients with osteochondritis dissecans of the knee, which was based on the presence of open or closed growth plates and the stability of osteochondral lesions, had excellent clinical results.

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Objective: The aim of this study was to assess the accuracy and reproducibility of aligning the cup trial with the transverse acetabular ligament (TAL) in total hip arthroplasty (THA) by using computer-assisted navigation and to determine whether the TAL was useful as a landmark in THA.
Methods: Between January 2011 and August 2012, 101 patients (108 hips) underwent primary THA using the posterolateral approach at our hospital. We measured the anatomical TAL anteversion intraoperatively by aligning the inferomedial rim of the cup trial with the TAL using computer-assisted navigation.
Results: The TAL was identified in 81.4% of cases (88 of 108 hips). Intra-observer reliability was high for both the expert surgeon (intraclass correlation coefficient [ICC(1.1)]=0.872) and the non-expert surgeons (ICC(1.1)=0.889). Inter-observer reliability was moderate (ICC(2.1)=0.614). The mean difference in the anatomical TAL anteversion measured by two surgeons was 6.7°±5.1° (range, 0.3°-21.3°). The mean anatomical TAL anteversion was 22.5°±8.5° (range, 7.7°-54.7°).
Conclusion: Some reports have suggested that the TAL can aid in positioning the cup in THA. In this study, we could identify the TAL in more than 80% of cases, and this ligament could be used to determine the anteversion of the cup in THA. Intra-observer reliability was high, and each surgeon was able to align the cup according to the TAL anteversion target. However, inter-observer reliability was only moderate. This is because the TAL is a short ligament with significant thickness, and the methods for aligning the cup trial with the TAL may differ among surgeons. TAL retroversion was not observed in any case. Therefore, the TAL was useful as a landmark for preventing the positioning of the cup in retroversion. However, in some cases with an excessive posterior pelvic tilt, the TAL anteversion may have been excessive and not necessarily optimal.

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Objective: Hydroxyapatite (HA) and beta-tricalcium phosphate (TCP) have been utilized as calcium phosphate-based bioceramics in various types of orthopedic surgery. Many basic studies have reported that these biomaterials have excellent osteoconductivity and/or absorbability properties under various experimental conditions. The purpose of this study was to clinically and radiologically compare the utility and osteoconductivity of TCP and HA spacers used in medial open-wedge high tibial osteotomy (HTO).
Methods: Thirty patients (31 knees) who underwent medial open-wedge HTO using a locked low-profile plate were followed up. In the first 19 knees, a wedged HA spacer was implanted in the opening space in HTO (Group H). In the remaining 12 knees, a wedged TCP spacer was implanted in the same manner (Group T). The patients underwent both clinical and radiological examinations before surgery and at 1 year after surgery.
Results: There were no statistical differences between the two groups with respect to preoperative background factors and there were no intra- or postoperative complications in either group. Osteoconductivity was assessed using the modified van Hemert's score. In Group T, the score was significantly higher (P=0.009) than that of Group H in the most medial osteotomy zone, while there were no significant differences between the two groups in the other zones. There were no statistical differences between Groups H and T with respect to the postoperative Japan Orthopaedic Society score, the femorotibial angle, the weight-bearing line, the tibial slope, and the Insall-Salvati ratio.
Conclusion: The present study demonstrated that TCP spacers are significantly superior to HA spacers in terms of osteoconductivity at 1 year after medial open-wedge HTO.

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