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骨关节炎软骨细胞中的PGC-1α:从作用机制到作用靶点

PGC-1α in osteoarthritic chondrocytes: From mechanism to target of action.

作者信息

Wang Haochen, Su Jianbang, Yu Minghao, Xia Yang, Wei Yingliang

机构信息

Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, China.

Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Front Pharmacol. 2023 Apr 6;14:1169019. doi: 10.3389/fphar.2023.1169019. eCollection 2023.

Abstract

Osteoarthritis (OA) is one of the most common degenerative joint diseases, often involving the entire joint. The degeneration of articular cartilage is an important feature of OA, and there is growing evidence that the mitochondrial biogenesis master regulator peroxisome proliferator-activated receptor coactivator 1α (PGC-1α) exert a chondroprotective effect. PGC-1α delays the development and progression of OA by affecting mitochondrial biogenesis, oxidative stress, mitophagy and mitochondrial DNA (mtDNA) replication in chondrocytes. In addition, PGC-1α can regulate the metabolic abnormalities of OA chondrocytes and inhibit chondrocyte apoptosis. In this paper, we review the regulatory mechanisms of PGC-1α and its effects on OA chondrocytes, and introduce potential drugs and novel nanohybrid for the treatment of OA which act by affecting the activity of PGC-1α. This information will help to further elucidate the pathogenesis of OA and provide new ideas for the development of therapeutic strategies for OA.

摘要

骨关节炎(OA)是最常见的退行性关节疾病之一,常累及整个关节。关节软骨退变是OA的一个重要特征,越来越多的证据表明线粒体生物合成的主要调节因子过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)具有软骨保护作用。PGC-1α通过影响软骨细胞中的线粒体生物合成、氧化应激、线粒体自噬和线粒体DNA(mtDNA)复制,延缓OA的发生和发展。此外,PGC-1α可调节OA软骨细胞的代谢异常并抑制软骨细胞凋亡。在本文中,我们综述了PGC-1α的调控机制及其对OA软骨细胞的影响,并介绍了通过影响PGC-1α活性来治疗OA的潜在药物和新型纳米杂化物。这些信息将有助于进一步阐明OA的发病机制,并为OA治疗策略的开发提供新思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76e0/10117990/2e8191d0c57f/fphar-14-1169019-g001.jpg

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