{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:35:53Z","timestamp":1792632953018,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T00:00:00Z","timestamp":1656374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20J14876"],"award-info":[{"award-number":["20J14876"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Entheses, which are tendon\u2010to\u2010bone attachment sites in the musculoskeletal system, play important roles in optimizing the mechanical stress and force transmitted from the muscle to the bone. Sports\u2010related enthesopathy shows pathological features, including hyperplasia of the fibrocartilage (FC) region in the enthesis. The amount of exercise and type of muscle contraction during movement is involved in the pathogenesis of sports\u2010related enthesopathy; however, the details of this condition are unclear. Here we examined the molecular pathways involved in the morphological changes of the muscle\u2013tendon\u2013enthesis complex and enthesis FC region in the supraspinatus muscle enthesis of mice under different exercise conditions. Following intervention, morphological changes in the muscle\u2013tendon\u2013enthesis complex were initiated in the eccentric contraction\u2010dominant exercise group at 2 weeks, with activation of the transforming growth factor\u2010\u03b2 (TGF\u03b2) superfamily pathway predicted by proteome and ingenuity pathway analyses. Histological and molecular biological analyses confirmed the activation of the TGF\u03b2\/bone morphogenetic protein (BMP)\u2010Smad pathway. The concentric contraction\u2010dominant exercise group showed no change in the morphology of the muscle\u2013tendon\u2013enthesis complex or activation of the TGF\u03b2\/BMP\u2010Smad pathway, despite overuse exercise. Statement of Clinical Significance: These results suggest that eccentric contraction\u2010dominant exercise induces sports\u2010related enthesopathy\u2010like morphological changes in the early stages as well as molecular biological changes, mainly in the transforming growth factor\u2010\u03b2 superfamily pathway in enthesis.<\/jats:p><jats:p><jats:bold>Statement of Clinical Significance<\/jats:bold>: These results suggest that eccentric contraction\u2010dominant exercise induces sports\u2010related enthesopathy\u2010like morphological changes in the early stages as well as molecular biological changes, mainly in the transforming growth factor\u2010\u03b2 superfamily pathway in enthesis.<\/jats:p>","DOI":"10.1002\/jor.25399","type":"journal-article","created":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T14:24:49Z","timestamp":1655562289000},"page":"511-523","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Eccentric contraction\u2010dominant exercise leads to molecular biological changes in enthesis and enthesopathy\u2010like morphological changes"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2231-7183","authenticated-orcid":false,"given":"Kaichi","family":"Ozone","sequence":"first","affiliation":[{"name":"Department of Health and Social Services, Health and Social Services Graduate School of Saitama Prefectural University Koshigaya Saitama Japan"},{"name":"Japan Society for the Promotion of Science Tokyo 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