细胞衰老在骨关节炎发病机制中的研究进展

Research progress of cellular senescence in the pathogenesis of osteoarthritis

目的综述细胞衰老在骨关节炎(osteoarthritis,OA)发生、发展中的病理作用及潜在治疗靶点。方法查阅国内外相关文献,对软骨细胞衰老、滑膜细胞衰老、MSCs衰老在OA中的作用及软骨细胞衰老发生的生物学机制和进展进行总结。结果现有证据已基本明确软骨细胞衰老、MSCs衰老与软骨修复异常及OA的发生、发展存在一定因果关系,而滑膜细胞衰老,特别是滑膜巨噬细胞衰老在OA中的作用尚不明确。转录因子、表观遗传是调控衰老上游通路的主要机制,细胞间的信号交流可促进健康细胞出现衰老表型。定向清除衰老细胞和促进MSCs年轻化可有效延缓OA的进展。结论细胞衰老是OA发生、发展中的重要生物学现象及潜在治疗靶点,深入研究其生物学机制有助于OA的早期防治。

Objective To review the pathological effects of cellular senescence in the occurrence and development of osteoarthritis(OA) and potential therapeutic targets. Methods The role of chondrocyte senescence,synovial cell senescence, mesenchymal stem cells senescence in OA, and the biological mechanism and progress of chondrocyte senescence were summarized by consulting relevant domestic and abroad literature. Results The existing evidence has basically made clear that chondrocyte senescence, mesenchymal stem cells senescence, and cartilage repair abnormalities, and the occurrence and development of OA have a certain causal relationship, and the role of the senescence of synovial cells, especially synovial macrophages in OA is still unclear. Transcription factors and epigenetics are the main mechanisms that regulate the upstream pathways of cellular senescence. Signal communication between cells can promote the appearance of senescent phenotypes in healthy cells. Targeted elimination of senescent cells and promotion of mesenchymal stem cells rejuvenation can effectively delay the progress of OA. Conclusion Cellular senescence is an important biological phenomenon and potential therapeutic target in the occurrence and development of OA. In-depth study of its biological mechanism is helpful to the early prevention and treatment of OA.