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

doi:10.1111/jcmm.14125

科研成果详情

题名	Melatonin ameliorates intervertebral disc degeneration via the potential mechanisms of mitophagy induction and apoptosis inhibition
作者	Chen, Yu 1,2; Wu, Yanqing 3; Shi, Hongxue2; Wang, Jianle 1; Zheng, Zengming1; Chen, Jian 1; Chen, Xibang 1; Zhang, Zengjie 1; Xu, Daoliang1; Wang, Xiangyang1; Xiao, Jian1,2
发表日期	2019-03
发表期刊	JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	apoptosis intervertebral disc degeneration melatonin mitophagy oxidative stress
其他关键词	NUCLEUS PULPOSUS CELLS ; OXIDATIVE STRESS ; PARKIN ; MITOCHONDRIA ; PROTECTS ; INJURY ; DEATH ; MODEL
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.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81871807, 81722028, R18H150001]; Zhejiang Provincial Natural Science FoundationNatural Science Foundation of Zhejiang Province
出版者	WILEY
出版地	HOBOKEN
ISSN	1582-4934
EISSN	1582-4934
卷号	23 期号:3 页码:2136-2148
DOI	10.1111/jcmm.14125
页数	13
WOS类目	Cell Biology ; Medicine, Research & Experimental
WOS研究方向	Cell Biology ; Research & Experimental Medicine
WOS记录号	WOS:000458920000045
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	30609271
PMC记录号	PMC6378230
SCOPUSEID	2-s2.0-85061662549
通讯作者地址	[Wang, Xiangyang]Department of Orthopaedic Surgery,The Second Afliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Molecular Medicine;Cell Biology
TOP期刊	TOP期刊
引用统计	被引频次：40[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/17171
专题	药学院（分析测试中心）_生物制药系_生物制药工程第二临床医学院、附属第二医院、育英儿童医院研究生工作部（研究生院）
通讯作者	Wang, Xiangyang
作者单位	1.Department of Orthopaedic Surgery,The Second Afliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou,China; 2.School of Pharmacy,Key Laboratory of Biotechnology and Pharmaceutical Engineering,Wenzhou Medical University,Wenzhou,China; 3.Institute of Life Sciences,Wenzhou University,Wenzhou,China
第一作者单位	温州医科大学; 药学院（分析测试中心）
通讯作者单位	温州医科大学
第一作者的第一单位	温州医科大学
推荐引用方式 GB/T 7714	Chen, Yu,Wu, Yanqing,Shi, Hongxue,et al. Melatonin ameliorates intervertebral disc degeneration via the potential mechanisms of mitophagy induction and apoptosis inhibition[J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2019,23(3):2136-2148.
APA	Chen, Yu., Wu, Yanqing., Shi, Hongxue., Wang, Jianle., Zheng, Zengming., ... & Xiao, Jian. (2019). Melatonin ameliorates intervertebral disc degeneration via the potential mechanisms of mitophagy induction and apoptosis inhibition. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 23(3), 2136-2148.
MLA	Chen, Yu,et al."Melatonin ameliorates intervertebral disc degeneration via the potential mechanisms of mitophagy induction and apoptosis inhibition".JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 23.3(2019):2136-2148.