{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:21:05Z","timestamp":1788326465459,"version":"build-2803163510"},"reference-count":137,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["PNRR-MAD-2022-12376898"],"award-info":[{"award-number":["PNRR-MAD-2022-12376898"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["F83C22002480001"],"award-info":[{"award-number":["F83C22002480001"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"award":["PNRR-MAD-2022-12376898"],"award-info":[{"award-number":["PNRR-MAD-2022-12376898"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]},{"award":["F83C22002480001"],"award-info":[{"award-number":["F83C22002480001"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Funct. Morphol. Kinesiol.","JFMK"],"abstract":"<jats:p>Osteoarthritis (OA) is a leading cause of disability worldwide, characterized by progressive joint degeneration driven by extracellular matrix (ECM) breakdown, chondrocyte apoptosis, and chronic low-grade inflammation. Despite the availability of several pharmacological and non-pharmacological interventions, no current therapy effectively halts or reverses disease progression. Physical activity is traditionally recognized as a cornerstone in OA management, improving pain and functional outcomes; however, the molecular mechanisms underlying its beneficial effects remain partially understood. Irisin, a myokine generated by proteolytic cleavage of fibronectin type III domain-containing protein 5 in response to muscle contraction, has recently emerged as a potential regulator of cartilage homeostasis. Experimental evidence indicates that irisin exerts pleiotropic effects by modulating inflammatory and catabolic signaling pathways, promoting anabolic and reparative processes, restoring autophagic and mitophagic flux, and preserving mitochondrial function. These actions collectively contribute to the maintenance of ECM integrity and chondrocyte viability. In vitro and in vivo studies consistently support the protective role of irisin in cartilage biology, highlighting its involvement in the muscle\u2013cartilage axis and its potential as both a biomarker and therapeutic target for OA. This narrative review critically evaluates the chondrocyte-specific mechanisms, receptor uncertainties, experimental-model limitations, analytical challenges, and delivery strategies that currently define the biological and translational relevance of irisin in OA. Particular attention is given to the identification of irisin-mediated signaling pathways in chondrocytes, optimization of delivery strategies, and the definition of exercise regimens capable of maximizing its chondroprotective effects.<\/jats:p>","DOI":"10.3390\/jfmk11030343","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:21:19Z","timestamp":1788168079000},"page":"343","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Irisin in Cartilage Homeostasis: Molecular Mechanisms and Therapeutic Implications for Osteoarthritis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3305-6434","authenticated-orcid":false,"given":"Raffaella Rosy","family":"Vescio","sequence":"first","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Operative Research Unit of Laboratory, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morena Francesca","family":"Fiordalisi","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Ambrosio","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Research Unit of Orthopaedic and Trauma Surgery, Departmental Faculty of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Fiorentino","sequence":"additional","affiliation":[{"name":"Research Unit of Orthopaedic and Trauma Surgery, Departmental Faculty of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9535-6582","authenticated-orcid":false,"given":"Elisabetta","family":"de Rinaldis","sequence":"additional","affiliation":[{"name":"Research Unit of Orthopaedic and Trauma Surgery, Departmental Faculty of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Di Giacomo","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8566-8952","authenticated-orcid":false,"given":"Fabrizio","family":"Russo","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Research Unit of Orthopaedic and Trauma Surgery, Departmental Faculty of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Denaro","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7142-1660","authenticated-orcid":false,"given":"Gianluca","family":"Vadal\u00e0","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Research Unit of Orthopaedic and Trauma Surgery, Departmental Faculty of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Papalia","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Research Unit of Orthopaedic and Trauma Surgery, Departmental Faculty of Medicine and Surgery, 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