Melatonin and/or therapeutic exercise induces autophagy‐mediated muscles remodeling in collagenase‐induced osteoarthritic rats

Osteoarthritis (OA) is characterized by progressive degeneration of arthritic cartilage, subsequent joint narrowing, and abnormal gait. The purpose of this study is to determine the effects of melatonin and/or exercise on the muscle remodeling and functional gait in collagenase‐induced OA rats. Melatonin (MT) injection was performed twice/day subcutaneously. The treadmill exercise (Ex) was conducted for 1‐hr/day at the frequency of 5 days/week. As results, body weight was significantly reduced by melatonin and/or exercise (P<.05), whereas no significance was shown in gastrocnemius as well as tibialis anterior muscle mass in OA+MT and OA+MT+Ex group at day 28. MAFbx, ubiquitin E3 ligase, was increased in medial gastrocnemius muscle in OA+MT+Ex group at day 7 (P<.05). Intervention also induced an upregulation of autophagic molecules, LC3 and BECN1 (P<.05). At day 28, the relative distribution of MHC1b was significantly increased in gastrocnemius muscle of OA+MT and OA+MT+Ex groups (P<.05). Sarcomeric Nebulin was increased by melatonin and/or treadmill exercise at day 28 (P<.05). Furthermore, as a result of footprint, intervention increased feet contact area. Taken together, melatonin and/or exercise activated autophagic machinery inducing muscle structural remodeling in collagenase‐induced OA rats.