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Their loss\/dysfunction has been associated with aging, injury, and osteoarthritis (OA), which is characterized by cartilage degradation. However, the role of chondrocyte death in cartilage degeneration remains controversial. We employed a Cre\u2010inducible diphtheria toxin mouse model to deplete articular chondrocytes and evaluated the spatiotemporal effects on tissue structure and functional integrity. Chondrocyte\u2010ablated mice exhibit altered proteoglycan staining, mechanical properties, and transient upregulation of proteases. Despite overt hypocellularity in aged mice, the phenotype did not progress to cartilage degeneration, nor OA. Our results suggest that murine articular cartilage has the ability, albeit limited, to compensate for the loss of chondrocytes and mitigate the consequent degree of harm. We demonstrate that chondrocyte depletion in the absence of injury, inflammation, or other insult is insufficient to initiate the OA disease cascade.<\/jats:p>","DOI":"10.1096\/fj.202500883r","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T10:50:09Z","timestamp":1755773409000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Induced Chondrocyte Ablation Disrupts Articular Cartilage Homeostasis but Is Not a Driver of Degeneration"],"prefix":"10.1096","volume":"39","author":[{"given":"Anand O.","family":"Masson","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Calgary  Calgary Alberta Canada"},{"name":"McCaig Institute for Bone and Joint Health University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica M.","family":"Corpuz","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Calgary  Calgary Alberta Canada"},{"name":"McCaig Institute for Bone and Joint Health University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristian","family":"Corpuz","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Calgary  Calgary Alberta Canada"},{"name":"McCaig Institute for Bone and Joint Health University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-0698","authenticated-orcid":false,"given":"Jeff A.","family":"Biernaskie","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine University of Calgary  Calgary Alberta Canada"},{"name":"Alberta Children's Hospital Research Institute University of Calgary  Calgary Alberta Canada"},{"name":"Department of Surgery, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. 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