{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:16:44Z","timestamp":1762867004996,"version":"build-2065373602"},"reference-count":37,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Overuse\u2010induced muscle disorders (OIMD) frequently occur in athletes due to excessive and improper use under high physical demand, often leading to muscle pain and weakness. Limited studies have shown intramuscular fibrosis in OIMD, with fibro\u2010adipogenic progenitors (FAPs), also known as mesenchymal stromal cells (MSCs), playing a crucial role in this fibrosis. This study aimed to develop a rat OIMD model using neuromuscular electrical stimulation\u2010induced isometric exercise (NMES\u2010ISO) and to investigate mechanisms by which excessive exercise without adequate rest leads to OIMD. We hypothesize that daily NMES\u2010ISO would cause muscle weakness and fibrogenesis mediated by FAP activation triggered by muscle fiber damage. Male Wistar rats received daily NMES\u2010ISO loading on the plantar flexor muscles at a lengthened position. Two weeks of NMES\u2010ISO led to decreased muscle torque without muscle mass reduction. Masson\u2010Trichrome stain revealed collagen\u2010rich fibrogenic lesions in the gastrocnemius muscles, while Evans blue stain detected no muscle fiber damage during the first 5 days. MRI showed increased T2*wi signals correlating with fibrogenic areas. Excessive NMES\u2010ISO stimulated FAP proliferation. This study established a rat model of OIMD using NMES\u2010ISO, characterized by muscle weakness and intramuscular fibrogenesis. Contrary to our hypothesis, FAP activation occurred without overt muscle injury, suggesting excessive mechanical loading may directly trigger FAP proliferation and fibrogenesis. It was cautioned that even relatively safe isometric contraction training could lead to FAP activation and intramuscular fibrosis without proper methods and recovery periods.<\/jats:p>","DOI":"10.1002\/jor.70076","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T14:18:35Z","timestamp":1759241915000},"page":"2102-2113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Overuse\u2010Induced Muscle Disorder: Establishing a Rat Model to Unravel the Role of Fibro\u2010Adipogenic Progenitor Cells in Intramuscular Fibrosis"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8322-463X","authenticated-orcid":false,"given":"Hiroyori","family":"Fusagawa","sequence":"first","affiliation":[{"name":"San Francisco Veterans Affairs Health Care System San Francisco California USA"},{"name":"Department of Orthopaedic Surgery University of California San Francisco  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