{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T08:47:24Z","timestamp":1767689244759,"version":"3.48.0"},"reference-count":110,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020419","name":"Cure-CMD","doi-asserted-by":"crossref","award":["2023-2025"],"award-info":[{"award-number":["2023-2025"]}],"id":[{"id":"10.13039\/100020419","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Italian Ministry of University and Research","award":["MUR-PRIN 2022MXH3JY"],"award-info":[{"award-number":["MUR-PRIN 2022MXH3JY"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Collagen VI-related myopathies (COL6-RM) encompass a spectrum of disorders characterized by muscle weakness, joint contractures, and connective tissue abnormalities resulting from mutations in the collagen VI genes. While muscle pathology has been extensively studied, tendon dysfunction has emerged as a critical yet underexplored contributor to disease severity, particularly in the development of joint contractures. Tendons from patients and animal models show disrupted collagen fibrillogenesis, altered extracellular matrix (ECM) composition, and impaired cellular mechanotransduction. Various defects in ECM remodeling pathways further exacerbate tendon pathology. Importantly, current clinical management remains limited to orthopedic interventions with modest outcomes, and targeted pharmacological strategies or gene-editing therapies are not yet available for clinical application. Therefore, understanding the basic pathogenic mechanisms underlying tendon dysfunction is essential for identifying novel therapeutic targets. This review provides a comprehensive synthesis of current understanding and recent advances concerning the role of mutated collagen VI in cellular and molecular mechanisms underlying tendon dysfunction. Emphasis is placed on the role of mutated collagen VI in the modulation of key signaling pathways related to mechanotransduction and primary cilium function in COL6-RM. By discussing these multifaceted contributions to disease pathogenesis, this review outlines future research directions in the field and highlights potential pathways for targeted therapeutic interventions.<\/jats:p>","DOI":"10.3390\/ijms262412014","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T09:36:39Z","timestamp":1765791399000},"page":"12014","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tendon Dysfunction in Collagen VI-Related Myopathies: Novel Mechanistic Insights with Therapeutic Potential"],"prefix":"10.3390","volume":"26","author":[{"given":"Patrizia","family":"Sabatelli","sequence":"first","affiliation":[{"name":"CNR-Institute of Molecular Genetics, 40136 Bologna, Italy"},{"name":"IRCCS, Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0716-4951","authenticated-orcid":false,"given":"Alberto","family":"Di Martino","sequence":"additional","affiliation":[{"name":"1st Orthopedics and Traumatology Department, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"},{"name":"Department of Biomedical and Neuromotor Science, DIBINEM, University of Bologna, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8152-4778","authenticated-orcid":false,"given":"Cesare","family":"Faldini","sequence":"additional","affiliation":[{"name":"1st Orthopedics and Traumatology Department, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"},{"name":"Department of Biomedical and Neuromotor Science, DIBINEM, University of Bologna, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9571-8140","authenticated-orcid":false,"given":"Paolo","family":"Bonaldo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Padova, 35122 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1108-1198","authenticated-orcid":false,"given":"Luciano","family":"Merlini","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Science, DIBINEM, University of Bologna, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8062-1840","authenticated-orcid":false,"given":"Vittoria","family":"Cenni","sequence":"additional","affiliation":[{"name":"CNR-Institute of Molecular Genetics, 40136 Bologna, Italy"},{"name":"IRCCS, Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"key":"ref_1","first-page":"3525","article-title":"Collagen VI at a glance","volume":"128","author":"Cescon","year":"2015","journal-title":"J. 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