SIRT3 ameliorates osteoarthritis via regulating chondrocyte autophagy and apoptosis through the PI3K/Akt/mTOR pathway

被引：220

作者：

Xu, Kai ^{[1
]}

He, Yuzhe ^{[1
]}

Moqbel, Safwat Adel Abdo ^{[1
]}

Zhou, Xing ^{[1
]}

Wu, Lidong ^{[1
]}

Bao, Jiapeng ^{[1
]}

机构：

[1] Zhejiang Univ, Affiliated Hosp 2, Dept Orthoped Surg, Sch Med, Hangzhou, Peoples R China

来源：

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES | 2021年 / 175卷

基金：

中国国家自然科学基金;

关键词：

SIRT3; Osteoarthritis; Autophagy; Apoptosis; PI3K/Akt/mTOR signaling; ARTICULAR CHONDROCYTES; MITOCHONDRIAL FISSION; KNEE OSTEOARTHRITIS; SIGNALING PATHWAY; PROMOTES; PROLIFERATION; HOMEOSTASIS; INHIBITION; RATS;

D O I：

10.1016/j.ijbiomac.2021.02.029

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Osteoarthritis (OA) is the most common form of joint disease. The aim of this study was to explore the functions of SIRT3 on OA pathophysiology and the mechanism involved. Rat chondrocytes and destabilized medial meniscus (DMM) rat OA model were used as in vitro and in vivo models. In addition, lentivirus and plasmid were used to overexpress SIRT3, while siRNA was applied to establish SIRT3 knockdown. IL-1 beta induced inflammation, apoptosis, mitochondria' dysfunction, and chondrocyte degeneration were inhibited by SIRT3 overexpression, which were enhanced in SIRT3-knockdown rat chondrocytes. Furthermore, overexpression of SIRT3 could restore IL-1 beta-induced autophagy inhibition. We also found that IL-1 beta-induced PI3K/Akt/mTOR signaling pathway activation was inhibited by SIRT3 overexpression, which was enhanced by SIRT3 knockdown. Last, intra-articular SIRT3 overexpression alleviated the severity of OA-induced rat joint damage. Our results demonstrated that SIRT3 is an important protective agent against OA pathophysiology via inhibiting PI3K/Akt/mTOR signaling. (C) 2021 Elsevier B.V. All rights reserved.

引用

页码：351 / 360

页数：10

共 39 条

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