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These pathogenic variants result in elevated circulating levels of fibroblast growth factor 23 (FGF23), responsible for the main clinical manifestations of XLH, such as hypophosphatemia, skeletal deformities, and mineralization defects. However, XLH also involves muscular disorders (muscle weakness, pain, reduced muscle density, peak strength, and power). Although XLH is characterized by muscle disorders, to date there are few studies on the action of FGF23 on muscle. Therefore, this study aims to evaluate the effects of FGF23 in an in vitro model of skeletal muscle satellite cells derived from human biopsies (hSMCs). After isolating and characterizing three lines of hSMCs from three volunteers, we evaluated the effect of FGF23 on the proliferative and myogenic differentiation process. We observed that none of the three concentrations of FGF23 tested (1, 10, 100\u00a0ng\/mL) affected the proliferative process after 48\u00a0h of treatment. On the contrary, after 24 and 48\u00a0h of treatment, FGF23 resulted in a significant reduction in the gene expression of the myogenic regulatory factors family (Myf-5, MyoD-1, Myogenin, and MRF4), irisin, myosin heavy chain, myostatin, desmin, FGF23 receptors (FGRF1-4) and KLOTHO coreceptor. We, therefore, hypothesized that FGF23 is directly involved in the muscular disorders that characterize XLH, and clarifying these effects at the molecular and cellular level is essential to elucidate XLH pathogenesis and, consequently, its management.\n                  <\/jats:p>","DOI":"10.1007\/s00223-025-01415-4","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T18:38:41Z","timestamp":1757443121000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["X-Linked Hypophosphatemia: Role of Fibroblast Growth Factor 23 on Human Skeletal Muscle-Derived Cells"],"prefix":"10.1007","volume":"116","author":[{"given":"I.","family":"Falsetti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Palmini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Donati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Aurilia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Zonefrati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Di Filippo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Giustina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Giannini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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