p16INK4a downregulation alleviates temporomandibular joint osteoarthritis combined with type 2 diabetes by driving M2 polarization

IF 6.9 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy Pub Date : 2025-05-16 DOI:10.1016/j.biopha.2025.118172

Jilin Cai , Leqi Zhang , Qingqing Du , Moxu Wang , Xiaojie Ma , Yuyi Chen , Yuli Wang , Hua Yuan

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引用次数: 0

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.

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p16INK4a下调通过驱动M2极化缓解颞下颌关节骨性关节炎合并2型糖尿病

颞下颌关节骨关节炎（TMJOA）有时合并2型糖尿病（T2DM-TMJOA），对生活质量有限制作用，目前有效的治疗方案很少。因此，本项目试图确定p16INK4a （p16）在T2DM-TMJOA发展中的作用。在体内，p16基因敲除（P16KO）小鼠的髁突骨丢失较少，巨噬细胞极性从炎症M1改变为抗炎M2。在体外，在高糖和高棕榈油酸条件下，p16敲低（P16KD）或MS37452处理THP-1细胞分别抑制炎症血管生成和淋巴管生成，并支持成骨分化。从机制上讲，P16KD模型通过谷胱甘肽（GSH）恢复了线粒体功能，限制了细胞内铁积累，并使M2巨噬细胞极化。总的来说，这些数据确定p16是T2DM-TMJOA的关键调节因子，并为未来通过治疗性抑制p16的治疗策略提供证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomedicine & Pharmacotherapy 医学-药学

CiteScore

11.90

自引率

2.70%

发文量

1621

审稿时长

48 days

期刊介绍： Biomedicine & Pharmacotherapy stands as a multidisciplinary journal, presenting a spectrum of original research reports, reviews, and communications in the realms of clinical and basic medicine, as well as pharmacology. The journal spans various fields, including Cancer, Nutriceutics, Neurodegenerative, Cardiac, and Infectious Diseases.