Abstract
Temporomandibular joint osteoarthritis (TMJOA) is a disease that affects the TMJ and is associated with degenerative changes in the articular cartilage. Fibroblast-like synoviocytes (FLSs) have been found to contribute to osteoarthritis. Here, we aim to investigate the role of METTL3-mediated FLS senescence in the TMJOA process. TMJOA model rats were successfully generated, displaying typical structural and inflammatory alterations, and primary FLSs were isolated from monosodium iodoacetate (MIA)-induced TMJOA rats; these FLSs were accompanied by increased senescence, attenuated mitophagy, and upregulated METTL3. FLSs from TMJOA rats also induced cartilage degradation. Mechanistically, METTL3 silencing can increase PINK1 expression by increasing its RNA stability through m6A modification. In addition, we found that METTL3 silencing could delay cellular senescence and promote mitophagy by upregulating PINK1 in bleomycin (BLM)-induced hFLSs. Senescent FLSs can also accelerate pathological progression and cartilage degradation in Sprague–Dawley (SD) rats. This study revealed that METTL3 silencing could suppress the senescence of FLSs and promote mitophagy by mediating m6A modification to upregulate PINK1 during TMJOA progression, which might provide a theoretical basis for TMJOA therapy.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. The numerical source data underlying graphs in the manuscript can be found in the supplementary data file.
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Acknowledgements
The present study was supported in part by the National Natural Science Foundation of China (82470953) and the Natural Science Foundation of Sichuan Province (2025ZNSFSC0750).
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Conceptualization: L.X. and Y.M. Data curation: J.L., K.T., and Q.D. Formal analysis: L.X., J.L., and J.G. Funding acquisition: Y.M. and L.X. Investigation: J.L., W.L., X.Y., and S.L. Methodology: L.X. and K.T. Project administration: L. X. and J.L. Visualization: L.X. and K.T. Writing - original draft: L.X. and Y.M. Writing - review & editing: All authors.
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Tian, K., Du, Q., Guo, J. et al. METTL3-mediated fibroblast-like synoviocytes senescence promotes temporomandibular joint osteoarthritis progression. Commun Biol (2026). https://doi.org/10.1038/s42003-026-09773-x
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DOI: https://doi.org/10.1038/s42003-026-09773-x
