SIRT3 Activation by Dihydromyricetin Suppresses Chondrocytes Degeneration via Maintaining Mitochondrial Homeostasis

被引：88

作者：

Wang, Jianle ^{[1
,2
,3
]}

Wang, Ke ^{[1
,2
,3
]}

Huang, Chongan ^{[1
,2
,3
]}

Lin, Dongdong ^{[1
,2
]}

Zhou, Yifei ^{[1
,2
,3
,5
]}

Wu, Yaosen ^{[1
,2
,3
,5
]}

Tian, Naifeng ^{[1
,2
,3
,5
]}

Fan, Pei ^{[1
,2
]}

Pan, Xiangxiang ^{[1
,2
,3
]}

Xu, Daoliang ^{[1
,2
]}

Hu, Jianing ^{[5
]}

Zhou, Ying ^{[5
]}

Wang, Xiangyang ^{[1
,2
,3
,5
]}

Zhang, Xiaolei ^{[1
,2
,3
,4
,5
]}

机构：

[1] Wenzhou Med Univ, Dept Orthopaed, Affiliated Hosp 2, 109 Xueyuan Xi Rd, Wenzhou 325027, Zhejiang, Peoples R China

[2] Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325027, Zhejiang, Peoples R China

[3] Zhejiang Prov Key Lab Orthopaed, Wenzhou 325027, Zhejiang, Peoples R China

[4] Chinese Orthopaed Regenerat Med Soc, Wenzhou, Peoples R China

[5] Wenzhou Med Univ, Sch Med 2, Wenzhou, Peoples R China

来源：

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2018年 / 14卷 / 13期

基金：

中国国家自然科学基金;

关键词：

Dihydromyricetin; osteoarthritis; mitochondria; SIRT3; OXIDATIVE STRESS; SMALL-MOLECULE; PROMOTES; OSTEOARTHRITIS; DEACETYLATION; ACETYLATION; SENESCENCE; PATHWAY; ALPHA; RATS;

D O I：

10.7150/ijbs.27746

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：

Mitochondrial dysfunction is an important contributor to the development of osteoarthritis (OA). Sirtuin 3 (SIRT3) regulates diverse mitochondrial proteins to maintain mitochondrial homeostasis, and dihydromyricetin (DHM) is reported as a potential SIRT3 activator. This study aims to explore the relevance of SIRT3 and OA, as well as the therapeutic effects of DHM on mitochondrial homeostasis in TNF-alpha-treated chondrocytes. The relationship between SIRT3 and OA was confirmed by detecting SIRT3 level in vitro and in vivo. Mitochondrial dysfunction was evaluated in chondrocytes with or without SIRT3 knockdown. Furthermore, the effects of DHM on mitochondrial homeostasis were performed in TNF-alpha-treated rat chondrocytes in vitro. In this study, our results showed that the SIRT3 level was decreased in mouse OA cartilage, corresponding to the reduced SIRT3 level in TNF-alpha-treated chondrocytes in vitro. SIRT3 knockdown induced mitochondrial dysfunction in chondrocytes. Moreover, our study demonstrated that DHM might activate SIRT3 to protect rat chondrocytes from TNF-alpha-induced degeneration and protective effects of DHM on mitochondrial homeostasis in chondrocytes attributed to enhanced SIRT3. Collectively, SIRT3 deficiency is implicated in OA development and DHM exerts anti-degeneration effect by maintaining mitochondrial homeostasis via a SIRT3-dependent manner in chondrocytes.

引用

页码：1873 / 1882

页数：10

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