{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:46:56Z","timestamp":1768506416626,"version":"3.49.0"},"posted":{"date-parts":[[2023,3,28]]},"group-title":"Pathology","reference-count":52,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,3,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Lack of dystrophin is the genetic basis for the Duchenne muscular dystrophy (DMD). However, disease severity varies between patients, based on specific genetic modifiers. D2-\n                  <jats:italic>mdx<\/jats:italic>\n                  is a model for severe DMD that exhibits exacerbated muscle degeneration and failure to regenerate even in the juvenile stage of the disease. We show that poor regeneration of juvenile D2-\n                  <jats:italic>mdx<\/jats:italic>\n                  muscles is associated with enhanced inflammatory response to muscle damage that fails to resolve efficiently and supports excessive accumulation of fibroadipogenic progenitors (FAPs). Unexpectedly, the extent of damage and degeneration of juvenile D2-\n                  <jats:italic>mdx<\/jats:italic>\n                  muscle is reduced in adults and is associated with the restoration of the inflammatory and FAP responses to muscle injury. These improvements enhance myogenesis in the adult D2-\n                  <jats:italic>mdx<\/jats:italic>\n                  muscle, reaching levels comparable to the milder (B10-\n                  <jats:italic>mdx<\/jats:italic>\n                  ) mouse model of DMD.\n                  <jats:italic>Ex vivo<\/jats:italic>\n                  co-culture of healthy satellite cells (SCs) with the juvenile D2-\n                  <jats:italic>mdx<\/jats:italic>\n                  FAPs reduced their fusion efficacy and\n                  <jats:italic>in vivo<\/jats:italic>\n                  glucocorticoid treatment of juvenile D2 mouse improved muscle regeneration. Our findings indicate that aberrant stromal cell response contributes to poor myogenesis and greater muscle degeneration in dystrophic juvenile D2-\n                  <jats:italic>mdx<\/jats:italic>\n                  muscles and reversal of this reduces pathology in adult D2-\n                  <jats:italic>mdx<\/jats:italic>\n                  mouse muscle, identifying these as therapeutic targets to treat dystrophic DMD muscles.\n                <\/jats:p>","DOI":"10.1101\/2023.03.27.534413","type":"posted-content","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T21:40:20Z","timestamp":1680039620000},"source":"Crossref","is-referenced-by-count":0,"title":["Altered muscle niche contributes to myogenic deficit in the D2-\n                  <i>mdx<\/i>\n                  model of severe DMD"],"prefix":"10.64898","author":[{"given":"Davi A. 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