Melatonin ameliorates intervertebral disc degeneration via the potential mechanisms of mitophagy induction and apoptosis inhibition

被引：113

作者：

Chen, Yu ^{[1
,2
,3
]}

Wu, Yanqing ^{[4
]}

Shi, Hongxue ^{[3
]}

Wang, Jianle ^{[1
,2
]}

Zheng, Zengming ^{[1
,2
]}

Chen, Jian ^{[1
,2
]}

Chen, Xibang ^{[1
,2
]}

Zhang, Zengjie ^{[1
,2
]}

Xu, Daoliang ^{[1
,2
]}

Wang, Xiangyang ^{[1
,2
]}

Xiao, Jian ^{[1
,2
,3
]}

机构：

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

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

[3] Wenzhou Med Univ, Key Lab Biotechnol & Pharmaceut Engn, Sch Pharm, Wenzhou, Peoples R China

[4] Wenzhou Univ, Inst Life Sci, Wenzhou, Peoples R China

来源：

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE | 2019年 / 23卷 / 03期

基金：

中国国家自然科学基金;

关键词：

apoptosis; intervertebral disc degeneration; melatonin; mitophagy; oxidative stress; NUCLEUS PULPOSUS CELLS; OXIDATIVE STRESS; PARKIN; MITOCHONDRIA; PROTECTS; INJURY; DEATH; MODEL;

D O I：

10.1111/jcmm.14125

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Intervertebral disc degeneration (IDD) is a complicated disease in patients. The pathogenesis of IDD encompasses cellular oxidative stress, mitochondrion dysfunction and apoptosis. Melatonin eliminates oxygen free radicals, regulates mitochondrial homoeostasis and function, stimulates mitophagy and protects against cellular apoptosis. Therefore, we hypothesize that melatonin has beneficial effect on IDD by mitophagy stimulation and inhibition of apoptosis. The effects of melatonin on IDD were investigated in vitro and in vivo. For the former, melatonin diminished cellular apoptosis caused by tert-butyl hydroperoxide in nucleus pulposus (NP) cells. Mitophagy, as well as its upstream regulator Parkin, was activated by melatonin in both a dose and time-dependent manner. Mitophagy inhibition by cyclosporine A (CsA) partially eliminated the protective effects of melatonin against NP cell apoptosis, suggesting that mitophagy is involved in the protective effect of melatonin on IDD. In addition, melatonin was demonstrated to preserve the extracellular matrix (ECM) content of Collagen II, Aggrecan and Sox-9, while inhibiting the expression of matrix degeneration enzymes, including MMP-13 and ADAMTS-5. In vivo, our results demonstrated that melatonin treatment ameliorated IDD in a puncture-induced rat model. To conclude, our results suggested that melatonin protected NP cells against apoptosis via mitophagy induction and ameliorated disc degeneration, providing the potential therapy for IDD.

引用

页码：2136 / 2148

页数：13

共 52 条

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