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To investigate the role of ADAMTS5 in murine osteoarthritis (OA), resulting from destabilization of the medial meniscus (DMM model) or from TGFb1 injection and enforced uphill treadmill running (TTR model). Wild-type (WT) and ADAMTS5À/À mice were subjected to either DMM or TTR and joints were evaluated for meniscal damage, cartilage changes, and fibrotic ingrowths from the joint margins. Cartilage lesions were quantified on an 8-point scoring system. Cartilage chondroitin sulfate (CS) content was evaluated by SafraninO staining and by quantitative electrophoresis (FACE). The abundance of aggrecan, versican, and specific aggrecanase-generated products was determined by Western analysis. Joint changes were similar for WT mice taken through either the DMM or the TTR model. ADAMTS5 ablation essentially eliminated cartilage erosion and fibrous overgrowth in both models. In the TTR model, ADAMTS5 ablation did not eliminate aggrecanase activity from the articular cartilage but blocked fibrosis and resulted in the accumulation of aggrecan in the articular cartilage. The cartilage protection provided by ADAMTS5 ablation in the mouse does not result from prevention of aggrecanase activity per se, but it appears to be due to a blockade of joint tissue fibrosis and a concomitant increase in cartilage aggrecan content. ß

In this study, we compared acute and chronic bone marker and hormone responses to 6 weeks of low intensity (20% 1RM) blood flow restriction (BFR20) resistance training to high intensity (70% 1RM) traditional resistance training (TR70) and moderate intensity (45% 1RM) traditional resistance training (TR45) in young men (18–35 years). Participants were randomized to one of the training groups or to a control group (CON). The following training programs were performed 3 days per week for 6 weeks for knee extension and knee flexion exercises: BFR20, 20%1RM, 4 sets (30, 15, 15, 15 reps) wearing blood flow restriction cuffs around the proximal thighs; TR70, 70% 1RM 3 sets 10 reps; and TR45, 45% 1RM 3 sets 15 reps. Muscle strength and thigh cross-sectional area were assessed at baseline, between week 3 and 6 of training. Acute bone marker (Bone ALP, CTX-I) and hormone (testosterone, IGF-1, IGFBP-3, cortisol) responses were assessed at weeks 1 and 6, with blood collection done in the morning after an overnight fast. The main findings were that the acute bone formation marker (Bone ALP) showed significant changes for TR70 and BFR20 but there was no difference between weeks 1 and 6. TR70 had acute increases in testosterone, IGF-1, and IGFBP-3 (weeks 1 and 6). BFR20 had significant acute increases in testosterone (weeks 1 and 6) and in IGF-1 at week 6, while TR45 had significant acute increases in testosterone (week 1), IGF-1 (week 6), and IGFBP-3 (week 6). Strength and muscle size gains were similar for the training groups. In conclusion, low intensity BFR resistance training was effective for stimulating acute bone formation marker and hormone responses, although TR70 showed the more consistent hormone responses than the other training groups.

Context Military personnel engage in vigorous exercise, often resulting in higher bone mineral density; however, leg bone injuries occur frequently in this population. Predictors of change in tibial bone quality and strength need to be characterized in this high-risk population. Objectives To examine the effects of an 8-week military training intervention on total body and site-specific bone density and tibial bone quality, serum biomarkers (parathyroid hormone and sclerostin), body composition, and physical performance and to investigate which outcome variables (biomarkers, body composition, and physical performance) predict estimated tibial bone strength in college-aged Reserve Officers' Training Corps (ROTC) participants. Design Prospective cohort study. Setting University of Oklahoma. Patients or Other Participants The ROTC participants (14 males, 4 females) were matched for sex, age, and mass to physically active control participants (14 males, 4 females). The ROTC participants engaged in an 8-week training intervention, while the physically active control group made no changes to their exercise routines. Main Outcome Measure(s) Preintervention general health questionnaires were completed. Pre-, mid-, and postintervention bone scans (dual-energy x-ray absorptiometry and peripheral quantitative computed tomography); serum blood draws (parathyroid hormone and sclerostin); and physical performance measures (muscle strength and aerobic capacity) were obtained. Results The ROTC participants exhibited increased hip bone density mineral and content (both P values ≤ .02) after the 8-week intervention. Sclerostin, but not parathyroid hormone, was a positive correlate and predictor in all ROTC models for estimated bone strength at the fracture-prone 38% tibial site (ie, 38% of the tibial length proximal to the distal end of the tibia). Both groups displayed decreased total body and regional fat mass, and ROTC participants' aerobic capacity increased (all P values ≤ .05). Conclusions All bone, body composition, and performance measures either improved or were maintained in response to ROTC training. Sclerostin should be further investigated as a potential early indicator of changes in estimated tibial bone strength in military cohorts.