Mfn2 is involved in intervertebral disc degeneration through autophagy modulation

被引：93

作者：

Chen, Y. ^{[1
,2
,3
]}

Lin, J. ^{[1
,2
,3
]}

Chen, J. ^{[1
,2
,3
]}

Huang, C. ^{[1
,2
,3
]}

Zhang, Z. ^{[1
,2
,3
]}

Wang, J. ^{[1
,2
,3
]}

Wang, K. ^{[1
]}

Wang, X. ^{[1
,2
,3
]}

机构：

[1] Wenzhou Med Univ, Dept Orthopaed, Affiliated Hosp 2, Xueyuan Xi Rd, Wenzhou 325000, Zhejiang, Peoples R China

[2] Wenzhou Med Univ, Dept Orthopaed, Yuying Childrens Hosp, Wenzhou 325000, Zhejiang, Peoples R China

[3] Zhejiang Prov Key Lab Orthopaed, Wenzhou 325000, Zhejiang, Peoples R China

来源：

OSTEOARTHRITIS AND CARTILAGE | 2020年 / 28卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Mfn2; IVDD; Autophagic flux; mitophagy; Apoptosis; MITOFUSIN; 2; OXIDATIVE STRESS; NUCLEUS PULPOSUS; MITOCHONDRIAL DYSFUNCTION; MODEL; APOPTOSIS; MITOPHAGY; CELLS; DISEASE; DEATH;

D O I：

10.1016/j.joca.2019.12.009

中图分类号：

R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学（修复外科学）];

学科分类号：

100224 [整形外科学];

摘要：

Objective: To explore whether Mitofusin 2 (Mfn2) is implicated in the pathogenesis of intervertebral disc degeneration (IVDD). Methods: We detected the protein content of Mfn2 in degenerated human nucleus pulposus (NP) tissues and investigated the effects of Mfn2 knockdown and Mfn2 overexpression on rat nucleus pulposus cells (NPCs) under oxidative stress by using a range of biological techniques. Afterwards, we confirmed the effects of Mfn2 overexpression on NPCs in vivo and further evaluated the therapeutic action of adenovirus (AV)-Mfn2 injection in a rodent IVDD model. Results: Mfn2 expression was decreased in human NP tissues during IVDD. Mfn2 knockdown aggravated the impairment of autophagic flux, mitochondrial dysfunction and cellular apoptosis in rat NPCs after Tert-Butyl hydroperoxide (TBHP) treatment, while Mfn2 overexpression significantly reversed these alterations. Besides, Mfn2 overexpression promoted an ROS (reactive oxygen species)-dependent mitophagy via PINK1 (PTEN-induced putative kinase 1)/Parkin pathway in TBHP-treated NPCs. Inhibition of autophagy with chloroquine (CQ) disordered the protective effects of Mfn2 overexpression on NPCs. Furthermore, Mfn2 overexpression in discs by AV-Mfn2 injection ameliorated the development of IVDD in rats. Conclusion: Mfn2 repression is deeply involved in the pathogenesis of IVDD with its impairment on autophagy, leading to the aggravation of mitochondrial dysfunction and apoptotic cell death, which ought to be a promising therapeutic target for IVDD. (C) 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

引用

页码：363 / 374

页数：12

共 44 条

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