We aimed to investigate the effects of an anti-tumor necrosis factor-α antibody (ATNF) on cartilage and subchondral bone in a rat model of osteoarthritis. Twenty-four rats were randomly divided into three groups: sham-operated group (n=8); anterior cruciate ligament transection (ACLT)+normal saline (NS) group (n=8); and ACLT+ATNF group (n=8). The rats in the ACLT+ATNF group received subcutaneous injections of ATNF (20 μg/kg) for 12 weeks, while those in the ACLT+NS group received NS at the same dose for 12 weeks. All rats were euthanized at 12 weeks after surgery and specimens from the affected knees were harvested. Hematoxylin and eosin staining, Masson's trichrome staining, and Mankin score assessment were carried out to evaluate the cartilage status and cartilage matrix degradation. Matrix metalloproteinase (MMP)-13 immunohistochemistry was performed to assess the cartilage molecular metabolism. Bone histomorphometry was used to observe the subchondral trabecular microstructure. Compared with the rats in the ACLT+NS group, histological and Mankin score analyses showed that ATNF treatment reduced the severity of the cartilage lesions and led to a lower Mankin score. Immunohistochemical and histomorphometric analyses revealed that ATNF treatment reduced the ACLT-induced destruction of the subchondral trabecular microstructure, and decreased MMP-13 expression. ATNF treatment may delay degradation of the extracellular matrix via a decrease in MMP-13 expression. ATNF treatment probably protects articular cartilage by improving the structure of the subchondral bone and reducing the degradation of the cartilage matrix.

Purpose The present study investigated the recovery of performance and neuromuscular fatigue after cycling repeated sprints. Methods Ten participants performed two sessions of repeated sprints (one session: 10 × 10-s sprints, 30-s recovery) separated by 24 h (R24-S1 and R24-S2) and two sessions separated by 48 h (R48-S1 and R48-S2). The recovery condition (i.e., 24 or 48 h) was randomized and separated by 1 wk. All sessions were performed on a recumbent bike, allowing minimal delay between sprints termination and neuromuscular measurements. Neuromuscular function of knee extensors (neuromuscular assessment [NMA]) was assessed before sessions (presession), after the fifth sprint (midsession), and immediately after (postsession). Before sessions, baseline NMA was also carried out on an isometric chair. The NMA (bike and chair) was composed of maximal voluntary contraction (MVC) of knee extension and peripheral neuromuscular stimulation during the MVC and on relaxed muscle. Results The sprints performance was not significantly different between sessions and did not presented significant interaction between recovery conditions. MVC was significantly lower at R24-S2 compared with R24-S1 (-6.5% ± 8.8%, P = 0.038) and R48-S2 (-5.6% ± 8.2%, P = 0.048), whereas resting potentiated high-frequency doublet (Db100) was lower at R24-S2 compared with R24-S1 (-10.4 ± 8.3, P = 0.01) (NMA on chair). There were significant reductions in MVC (>30%, P < 0.001) and Db100 (>38%, P < 0.001) from pre- to postsession in all sessions, without significant interactions between recovery conditions (NMA on bike). Conclusion Cycling repeated sprints induce significant fatigue, particularly at the peripheral level, which is fully restored after 48 h, but not 24 h, of recovery. One versus two days of recovery does not affect neuromuscular fatigue appearance during cycling repeated-sprint sessions.

Osteoarthritis (OA) is the most common joint disease in humans. It affects the joint as a whole and is characterized by progressive articular cartilage destruction, abnormal subchondral bone remodelling, formation of osteophytes, ligament and periarticular muscle weakening and in some cases synovial inflammation, which ultimately lead to a painful and impaired joint. There are several known risk factors for the development of OA but the exact sequence of events that lead to the destruction of the articular cartilage is not yet fully understood. Hereditary hemochromatosis (HH), a disease caused by mutations in the HFE gene, is characterised by systemic iron overload, toxic accumulation of iron in parenchymal cells of liver, heart, and endocrine glands. It is also associated with musculoskeletal complications, namely an increased prevalence of OA. The role of iron overload in the development of OA is still undefined. To further understand the molecular mechanisms involved in the pathology of HHrelated OA, we surgically induced OA in the knee of a murine model of hereditary hemochromatosis and studied the changes to cartilage and bone. Also, in order to understand how the different mutations in the HFE gene affect systemic iron overload and related musculoskeletal complications, we studied the prevalence of musculoskeletal complications in a cohort of patients with different HH genotypes. Hfe-KO mice showed a systemic iron overload and an increased iron accumulation in the knee synovial membrane following surgery. The histological OA score was significantly higher in the Hfe-KO mice at 8 weeks after surgery. Micro-CT study of the proximal tibia revealed increased subchondral bone volume and increased trabecular thickness. Gene expression and immunohistochemical analysis showed a significant increase in the expression of matrix metallopeptidase 3 in the joints of Hfe-KO mice compared with control mice at 8 weeks after surgery. Among our cohort of HH patients the majority were homozygous for the C282Y mutation. The serum ferritin concentration and serum transferrin saturation at diagnosis were significantly higher in C282Y homozygous patients compared with those who were compound heterozygous (C282Y/H63D). Also the overall prevalence of self-reported musculoskeletal complications was significantly higher in patients with C282Y homozygosity. The findings of this study suggest that systemic iron overload does not cause OA directly but acts as a susceptibility factor. The systemic and synovial iron overload both contribute to increase the catabolic response of the articular cartilage to mechanical also suggests that the prevalence of musculoskeletal complications of HH is related to the magnitude of the iron overload, since there was a greater prevalence of OA in the homozygotes for the C282Y mutation, a genotype associated with higher systemic iron overload.