TNF-like weak inducer of apoptosis (TWEAK) is a type II membrane protein belonging to the TNF family that regulates apoptotic cell death, cellular proliferation, angiogenesis, and inflammation. However, the role of TWEAK in the pathogenesis of rheumatoid arthritis (RA) remains unclear. In this study, we have investigated the effect of neutralizing anti-TWEAK mAb on the development of collagen-induced arthritis (CIA), a well-established murine model of RA. Administration of anti-TWEAK mAb significantly ameliorated paw swelling, synovial hyperplasia, and infiltration of inflammatory cells. The levels of proinflammatory chemokines such as MCP-1 and MIP-2 in serum and knee joints were reduced by this treatment. Consistently, recombinant TWEAK enhanced the proliferation of MCP-1 and MIP-2 production by synovial cells from CIA mice in vitro. Histological examination also revealed that the treatment with anti-TWEAK mAb suppressed the development of small vessels in synovial tissues. These results indicated anti-inflammatory and antiangiogenic effects of the TWEAK blockade in CIA, which may be also beneficial for the treatment of RA.

BackgroundAthletes suffering from any injuries want to know when they will be able to return sports activity. The period of return-to-sport after the arthroscopic meniscectomy is still unknown. The aim of this study is to investigate the period of the return-to-sport from surgery and the clinical symptoms after the meniscectomy on stable knees.MethodsFifty-six athletes who underwent the arthroscopic meniscectomy were evaluated. The patients with an average age of 26.7 years (range, 13–67) comprised 45 men and 11 women, 16 medial meniscus and 40 lateral meniscus injuries. The average of the follow-up period was 9.2 months. The parameter examined were age, the injured side of meniscus (medial or lateral), articular cartilage status, amount of resection, and sports activity level.ResultsThe mean period was 54 days in young group, and was 89 days in old group (p = 0.0013). The period was 79 days in medial meniscus (MM) injured group, and was 61 days in lateral meniscus (LM) group (p = 0.017). There was a significant difference among the groups in activity levels and in amount of resection. Pain and/or effusion in the knee after the return-to-sport were found 22% of the MM group and 53% in the LM group.ConclusionsThe period of the return-to-sport was shorter in young age, high activity and large amount of resection group. Although athletes in LM group can return to sports earlier than those in MM group, more than half of athletes have pain or effusion at the time of return-to sport.

These data suggest that TWEAK/Fn14 interaction plays a substantial role in the synovitis of RA, by directly inducing the proliferation of SFs, and by up-regulating the production of inflammatory cytokines/chemokines as well as the expression of ICAM-1.

When children around 2 years of age show leg bowing and diseases are ruled out based on radiographic findings without conducting blood tests, they are classified as "physiologic" genu varum. Since whether or not physiologic genu varum is associated with bone metabolism is unclear, this study was conducted to clarify the association between genu varum and bone metabolism in children. Thirty-five pediatric patients with genu varm who visited our out-patient clinic were enrolled. While two of the 35 children had nutritional rickets, showing abnormalities on both blood test (ALP, ≥1000 IU/L; iPTH, >65 pg/mL and 25(OH)D, ≤20 ng/mL) and radiographs (such as cupping, fraying or splaying), five of 35 children showed abnormalities on blood tests but not radiographs. While metaphyseal-diaphyseal angle (MDA) correlated with serum 25-hydroxy vitamin D (r = -0.35, p = 0.04) and magnesium (r = -0.36, p = 0.04), MDA and femorotibial angle (FTA) correlated with alkaline phosphatase (r = 0.43, p = 0.01 and r = 0.51, p = 0.006, respectively). A ridge regression analysis adjusted for age and body mass index indicated that ALP was associated with MDA and FTA. A logistic regression analysis adjusted for age and BMI indicated that higher ALP influenced an MDA >11°, which indicates the risk for the progression of genu varum (odds ratio 1.002, 95% confidence interval 1.0003-1.003, p = 0.021). The higher ALP (+100 IU), the higher risk of an MDA >11° (odds ratio 1.22). In conclusion, genu varum is associated with the alkaline phosphatase level regardless of the presence of radiographic abnormalities in the growth plate in children.