p16INK4a downregulation alleviates temporomandibular joint osteoarthritis combined with type 2 diabetes by driving M2 polarization - 14/06/25
Abstract |
Temporomandibular joint osteoarthritis (TMJOA), sometimes combined with type 2 diabetes (T2DM-TMJOA), has a restricting effect on quality of life and currently has few efficacious treatment options. As such, this project sought to determine the role of p16INK4a (p16) in T2DM-TMJOA development. In vivo, p16 knockout (P16KO) mice experienced less condylar bone loss and altered macrophage polarities from the inflammatory M1 to anti-inflammatory M2. In vitro, p16 knockdown (P16KD) or MS37452 treatment of THP-1 cells under high glucose and high palmitoleic acid conditions inhibited inflammatory angiogenesis and lymphangiogenesis, and supported osteogenic differentiation, respectively. Mechanistically, P16KD modelling restored mitochondrial functionality, limited intracellular iron accumulation, and polarized M2 macrophages through glutathione (GSH). Collectively, these data identify p16 as a critical regulator of T2DM-TMJOA and provide evidence for a future treatment strategy by therapeutic inhibition of p16.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
P16KO and MS37452 reprogram macrophage polarization and ameliorate T2DM-TMJOA by promoting mitochondrial function and decreasing iron accumulation.
P16KO and MS37452 reprogram macrophage polarization and ameliorate T2DM-TMJOA by promoting mitochondrial function and decreasing iron accumulation.Le texte complet de cet article est disponible en PDF.
Highlights |
• | p16INK4a regulates T2DM-TMJOA progression via macrophage polarization. |
• | p16INK4a knockout shifts macrophages to an anti-inflammatory state. |
• | p16INK4a knockdown improves mitochondrial function and reduces iron accumulation. |
• | MS37452 is a promising therapeutic candidate for T2DM-TMJOA. |
• | p16INK4a is a novel therapeutic target for T2DM-TMJOA. |
Keywords : TMJ, OA, Iron overload, Mitochondria, p16INK4a, Macrophages
Plan
Vol 188
Article 118172- juillet 2025 Retour au numéro
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