The role of the sirtuin family in cartilage and osteoarthritis: molecular mechanisms and therapeutic targets.
The role of the sirtuin family in cartilage and osteoarthritis: molecular mechanisms and therapeutic targets.
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DOI：
10.1186/s13075-022-02983-8
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发表时间：
2022-12-31
影响因子：
4.9
通讯作者：
中科院分区：
文献类型：
--
作者：
骨关节炎（OA）的主要特征是关节软骨的进行性破坏。越来越多的研究表明，细胞外基质（ECM）稳态的破坏，软骨细胞代谢异常，衰老软骨细胞数量的增加和细胞死亡的异常激活，如软骨细胞凋亡和自噬，是OA发展的关键步骤。此外，线粒体功能障碍也参与了上述过程，是OA发病机制的关键因素。Sirtuin（SIRT）是一个依赖于NAD+的蛋白脱乙酰酶家族，在OA的病理生理过程中可以积极参与并主要调节软骨细胞的功能。位于线粒体中的SIRT家族的一些成员可以调节线粒体功能并通过脱乙酰化介导线粒体稳态以保护软骨细胞。此外，SIRT还可以通过发挥其脱乙酰化活性，维持ECM稳态，调节软骨细胞代谢，抑制软骨细胞凋亡和自噬，防止软骨中软骨细胞衰老。然而，SIRT家族对OA发病和发展的分子机制仍不清楚。本文就SIRT在OA进展中的潜在保护作用进行综述，并对几种SIRTuin激活分子及其在OA治疗中的应用进行综述。
Osteoarthritis (OA) is mainly characterized by the progressive destruction of articular cartilage. Mounting studies have revealed that disruption of extracellular matrix (ECM) homeostasis, aberrant chondrocyte metabolism, an increase in the number of senescent chondrocytes and abnormal activation of cell death such as chondrocyte apoptosis and autophagy, are the crucial steps in OA development. Additionally, mitochondrial dysfunction also participates in the abovementioned processes and is the key element of OA pathogenesis. Sirtuin (SIRT) is a family of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases that can actively participate and primarily regulate chondrocyte function in OA pathophysiological processes. Some members of the SIRT family located in mitochondria can regulate mitochondrial function and mediate mitochondrial homeostasis via deacetylation to protect chondrocytes. In addition, SIRT can maintain ECM homeostasis, regulate chondrocyte metabolism, inhibit chondrocyte apoptosis and autophagy, and prevent chondrocyte senescence in cartilage by exerting its deacetylation activity. However, the molecular mechanism of the SIRT family against the onset and development of OA remains poorly elucidated. In this review, we will discuss the potential protective role of SIRT in the progression of OA and summarize several sirtuin-activating molecules as well as their potential therapeutic applications for OA.
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影响因子：
7
作者：
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