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This study revealed a molecular link between macrophages and fibro\u2010adipogenic progenitors (FAPs) in both human subjects and mice via the transforming growth factor\u2010beta (TGF\u2010\u03b2)\u2010RUNX family transcription factor\u20102 (RUNX2) axis.\n                    <jats:italic>RUNX2<\/jats:italic>\n                    mRNA levels correlated positively with both the expression of fibrotic genes and the fibrosis area of MD patients. We demonstrated that specific ablation of RUNX2 in FAPs alleviated muscle fibrosis in an animal model of MD. Mechanistically, injured myofibers activated the transcription of chemokine genes, enhancing macrophage recruitment and the release of TGF\u2010\u03b2, which subsequently triggered RUNX2\u2010mediated transcription of fibrogenic genes in FAPs, promoting muscle fibrosis. Additionally, we demonstrated that CADD522, a RUNX2 inhibitor, protects against muscle fibrosis in both dystrophic and denervated mice. Importantly, the anti\u2010inflammatory drug prednisolone alleviated muscle fibrosis in MD patients by inhibiting inflammatory cytokine\u2010mediated RUNX2 activation. Collectively, our findings indicated that the TGF\u2010\u03b2\u2010RUNX2 axis is a viable target for alleviating muscle fibrosis and related diseases, highlighting potential future research directions.\n                  <\/jats:p>","DOI":"10.1002\/advs.202510850","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T06:18:38Z","timestamp":1766470718000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["RUNX2 Activation in Fibro\/Adipogenic Progenitors Promotes Muscle Fibrosis in Muscular Dystrophy"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7158-7804","authenticated-orcid":false,"given":"Pengkai","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery The First Affiliated Hospital of Anhui Medical University  Hefei Anhui China"},{"name":"MOE Innovation Center for Basic Research in Tumor Immunotherapy 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