The role of the sirtuin family in cartilage and osteoarthritis: molecular mechanisms and therapeutic targets

Arthritis Research & Therapy

Review

Jiawen Xu¹  Bin Shen¹  Yi Zeng¹  Limin Wu¹  Kaibo Sun¹  Yuangang Wu¹  Mingyang Li¹ 

[1] Department of Orthopedics Surgery, Orthopedic Research Institute, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China;

关键词: Osteoarthritis;    Sirtuin;    Cartilage destruction;    Chondrocyte;    Mitochondrial dysfunction;   

DOI  :  10.1186/s13075-022-02983-8

 received in 2022-07-08, accepted in 2022-12-20,  发布年份 2022

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s) 2022

【 图 表 】

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