{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:52:31Z","timestamp":1792417951357,"version":"4.4.0"},"reference-count":60,"publisher":"Wiley","issue":"58","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009110","name":"Natural Science Foundation of Xinjiang Uygur Autonomous Region","doi-asserted-by":"publisher","award":["2022D01D58"],"award-info":[{"award-number":["2022D01D58"]}],"id":[{"id":"10.13039\/100009110","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Sarcopenia, an age\u2010related degenerative disease of skeletal muscle, is closely associated with osteoporosis and other bone disorders, partly due to dysregulated endocrine function of skeletal muscle. However, the specific cellular sources and molecular mechanisms driving this pathological secretory phenotype remain poorly defined. Using three distinct aging murine models, including sedentary controls, treadmill exercise\u2010trained (TE) mice, and botulinum toxin A (BTXA)\u2010induced muscle atrophy, combined with human cohort analysis, we investigated muscle\u2010bone crosstalk. Fluorescence\u2010activated cell sorting (FACS) was used to isolate fibro\u2010adipogenic progenitors (FAPs). FAP\u2010specific genetic manipulations, including conditional knockout (cKO) mice and adeno\u2010associated virus\u2010mediated knockdown, together with pharmacological inhibition of YAP1, were employed to dissect the mechanistic link between muscle secretory dysfunction and bone metabolism. We demonstrate that pathogenic activation of FAPs serves as a critical cellular source of bone\u2010catabolic myokines during muscle atrophy. In a human cohort of older individuals with sarcopenia, osteoporosis, or osteosarcopenia, FAP numbers were significantly increased and correlated positively with sarcopenia traits and IL\u20106 and FGF21 levels. In mice, muscle wasting drives FAP accumulation through YAP1\u2010mediated mechanotransduction, characterized by enhanced proliferation, suppressed apoptosis, and acquisition of a profibrotic phenotype concomitant with elevated IL\u20106 and FGF21 secretion. Using FAP\u2010specific Il6 or Fgf21 knockdown, we showed that genetic ablation of these myokines in FAPs rescued trabecular bone loss despite persistent muscle atrophy. Mechanistically, YAP1 functions as a central regulator of this pathogenic secretory phenotype; FAP\u2010specific\n                    <jats:italic>Yap1<\/jats:italic>\n                    overexpression may contribute to the myokine dysfunction and bone loss, while FAP\u2010specific\n                    <jats:italic>Yap1<\/jats:italic>\n                    deletion or pharmacological inhibition diminished bone\u2010loss\u2010related myokine production and ameliorated bone deterioration. FAP\u2010specific Yap1 cKO mice demonstrated that endogenous YAP1 is essential for pathogenic FAP activation and subsequent bone loss. Furthermore, therapeutic targeting of the FAP\u2010YAP1\u2010myokine axis provided robust skeletal protection in ovariectomy\u2010induced postmenopausal osteoporosis. These findings reveal that dysregulated endocrine function of skeletal muscle promotes bone loss through YAP1\u2010driven pathogenic FAPs secreting IL\u20106 and FGF21, identifying FAP\u2010derived IL\u20106 and FGF21 as key mediators of muscle\u2010bone crosstalk and establishing the YAP1\u2010FAP\u2010myokine axis as a therapeutic target for preventing bone loss in sarcopenia and osteoporosis.\n                  <\/jats:p>","DOI":"10.1002\/advs.76788","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T12:23:38Z","timestamp":1785155018000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["YAP1\u2010Driven Pathogenic Fibro\u2010Adipogenic Progenitors Secrete IL\u20106 and FGF21 to Mediate Muscle\u2010Bone Crosstalk and Promote Bone Loss"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4832-3594","authenticated-orcid":false,"given":"Xiaoyu","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Spine Surgery The First Affiliated Hospital of Xinjiang Medical University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The First Affiliated Hospital of Xinjiang Medical University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Ma","sequence":"additional","affiliation":[{"name":"Endocrinology Department The First Affiliated Hospital of Xinjiang Medical University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weikun","family":"Meng","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Institute Department of Orthopaedics West China Hospital Sichuan 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