{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:46:18Z","timestamp":1792197978509,"version":"4.4.0"},"reference-count":41,"publisher":"Wiley","issue":"39","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFF1000602"],"award-info":[{"award-number":["2021YFF1000602"]}],"id":[{"id":"10.13039\/501100012166","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":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Disuse\u2010induced muscle atrophy remains a therapeutic challenge due to its complex etiology. Osteocalcin (OCN) is a bone\u2010derived hormone with metabolic functions, while its role in muscle atrophy remains poorly understood. Here, we identified a mechanosensitive Piezo1\/osteocalcin\/Irisin axis linking bone mechanotransduction to muscle homeostasis. We showed that bilateral hindlimb immobilization (IMM) markedly reduced circulating undercarboxylated OCN. OCN deficiency exacerbated IMM\u2010induced muscle atrophy, whereas exogenous OCN attenuated muscle atrophy and promoted recovery. Mechanistically, Piezo1 acted as an upstream regulator of OCN, as pharmacological Piezo1 activation attenuated muscle atrophy in an OCN\u2010dependent manner, whereas bone\u2010specific Piezo1 knockdown abolished these protective effects. Furthermore, OCN exerted protective effects through the muscle receptor Gprc6a and the downstream effector Fndc5\/Irisin, muscle\u2010specific knockdown of either Gprc6a or Fndc5 abolished OCN\u2010mediated protective effects. Notably, pair\u2010feeding experiments demonstrated that OCN directly protects against muscle atrophy independent of increased food intake. Finally, we demonstrated functional conservation of this axis in porcine myotubes. Notably, only animal models were used in the current study, and future studies are needed to test if the signaling axis has relevance to humans. Collectively, this work establishes that the Piezo1\/Osteocalcin\/Irisin axis mediates mechanical unloading\u2010induced muscle atrophy and highlights this axis as a promising therapeutic target for disuse\u2010induced muscle atrophy.<\/jats:p>","DOI":"10.1002\/advs.75355","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T11:50:03Z","timestamp":1776426603000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mechanosensitive Piezo1\/Osteocalcin\/Irisin Axis Protects Against Disuse\u2010Induced Muscle Atrophy"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7617-1728","authenticated-orcid":false,"given":"Zhaolu","family":"Wang","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology Northwest A&amp;F University  Yangling 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