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However, most DMD mouse model studies have focused on limb and respiratory muscles, showing an extensive wave of muscle necrosis-regeneration in juveniles followed by a low-intensity chronic disease in adults. In the present study, we investigated the impact of DMD on the masseter muscles in mice and observed persistence and progression of the conditions at least until 12\u00a0months of age. Masseter and limb muscles from <jats:italic>mdx<\/jats:italic>\n            <jats:sup>\n              <jats:italic>5Cv<\/jats:italic>\n            <\/jats:sup> mice aged 3, 6, and 12\u00a0months were compared with those from control mice (C57BL\/6\u00a0J background), measuring levels of necrosis, regeneration, inflammation, and fibrosis. In addition, mRNA expression of markers associated with fibrosis and transforming growth factor-beta (TGF-\u03b2) signalling were examined. Our findings revealed that regeneration and inflammation were increased in dystrophic masseter muscles at 3\u00a0months of age and persisted to older ages. Fibrosis was more pronounced in the dystrophic masseter muscles at 6\u00a0months of age and revealed an increase of the fibro-adipogenic progenitor cell population. Notably, we found elevated deposition of fibronectin and TGF-\u03b2 in fibrotic foci of the dystrophic masseter muscles. Increased TGF-\u03b2 signalling was confirmed by a significant increase in nuclear localization of phosphorylated SMAD2 in dystrophic masseter and limb muscles. Our results suggest that masseter muscles may exhibit more sustained dystrophic damage than locomotor muscles. We speculate that any therapeutic developed for DMD may be of benefit to orofacial tissues, although their efficacy remain to be established.<\/jats:p>","DOI":"10.1038\/s41598-025-17154-3","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T15:48:11Z","timestamp":1759160891000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Persistent tissue regeneration and transforming growth factor-\u03b2 induced fibrosis in the masseter muscle of mdx5Cv mice"],"prefix":"10.1038","volume":"15","author":[{"given":"Aouatef","family":"Ait-Lounis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence A.","family":"Neff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stavros","family":"Kiliaridis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Wehrle-Haller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier M.","family":"Dorchies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory S.","family":"Antonarakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"17154_CR1","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1016\/j.nmd.2014.03.008","volume":"24","author":"JK Mah","year":"2014","unstructured":"Mah, J. 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