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In this study, we uncover a previously unrecognized mechanism by which the extracellular matrix protein TGFBI (TGF\u2010\u03b2\u2010induced) sustains condylar fibrocartilage homeostasis by restraining protein O\u2010GlcNAcylation. We demonstrate that TGFBI is predominantly expressed in the condylar perichondrium and is markedly downregulated in both TMJOA patients and corresponding mouse models. Genetic ablation of\n                    <jats:italic>Tgfbi<\/jats:italic>\n                    delays postnatal skeletal development, promotes chondrocyte hypertrophy, and accelerates fibrocartilage degeneration. Mechanistically, TGFBI functions as a negative regulator of O\u2010GlcNAcylation in condylar perichondrial cells (cPCs), thereby suppressing both the transcriptional activation and protein stability of the matrix protease ADAMTS16. Notably, ex vivo studies identify Ser1170 of ADAMTS16 as a critical O\u2010GlcNAcylation site that directly governs its protein turnover. By inhibiting O\u2010GlcNAcylation at this residue, TGFBI prevents condylar chondrocyte hypertrophy, senescence, and extracellular matrix degradation. Collectively, our findings establish the TGFBI\u2013O\u2010GlcNAcylation\u2013ADAMTS16 axis as a vital driver of condylar fibrocartilage degeneration and highlight a promising metabolic target for TMJOA therapy.\n                  <\/jats:p>","DOI":"10.1002\/advs.77594","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:39:04Z","timestamp":1789619944000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TGFBI Maintains Fibrocartilage Homeostasis by Restraining O\u2010GlcNAcylation to Inactivate and Destabilize ADAMTS16 in Temporomandibular Joint Osteoarthritis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6809-3931","authenticated-orcid":false,"given":"Xin","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration Hubei Key Laboratory of Stomatology Key Laboratory of Oral Biomedicine Ministry of Education School &amp; 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