Metformin protects against apoptosis and senescence in nucleus pulposus cells and ameliorates disc degeneration in vivo

doi:10.1038/cddis.2016.334

科研成果详情

题名	Metformin protects against apoptosis and senescence in nucleus pulposus cells and ameliorates disc degeneration in vivo
作者	Chen, Deheng 1,2; Xia, Dongdong 1,2,3; Pan, Zongyou 1,2; Xu, Daoliang1,2; Zhou, Yifei1,2; Wu, Yaosen1,2; Cai, Ningyu 1,2; Tang, Qian 1,2; Wang, Chenggui1,2; Yan, Meijun 3; Zhang, Jing Jie 3; Zhou, Kailiang 1,2; Wang, Quan 1,2; Feng, Yongzeng1,2; Wang, Xiangyang1,2; Xu, Huazi1,2; Zhang, Xiaolei1,2,4; Tian, Naifeng1,2
发表日期	2016-10
发表期刊	CELL DEATH & DISEASE 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	LOW-BACK-PAIN ; OXIDATIVE STRESS ; INTERVERTEBRAL DISCS ; AUTOPHAGY ; PATHWAY ; DEATH ; ACTIVATION ; INHIBITION ; INDUCTION ; MTOR
摘要	Intervertebral disc degeneration (IDD) is a complicated process that involves both cellular apoptosis and senescence. Metformin has been reported to stimulate autophagy, whereas autophagy is shown to protect against apoptosis and senescence. Therefore, we hypothesize that metformin may have therapeutic effect on IDD through autophagy stimulation. The effect of metformin on IDD was investigated both in vitro and in vivo. Our study showed that metformin attenuated cellular apoptosis and senescence induced by tert-butyl hydroperoxide in nucleus pulposus cells. Autophagy, as well as its upstream regulator AMPK, was activated by metformin in nucleus pulposus cells in a dose-and time-dependent manner. Inhibition of autophagy by 3-MA partially abolished the protective effect of metformin against nucleus pulposus cells' apoptosis and senescence, indicating that autophagy was involved in the protective effect of metformin on IDD. In addition, metformin was shown to promote the expression of anabolic genes such as Col2a1 and Acan expression while inhibiting the expression of catabolic genes such as Mmp3 and Adamts5 in nucleus pulposus cells. In vivo study illustrated that metformin treatment could ameliorate IDD in a puncture-induced rat model. Thus, our study showed that metformin could protect nucleus pulposus cells against apoptosis and senescence via autophagy stimulation and ameliorate disc degeneration in vivo, revealing its potential to be a therapeutic agent for IDD.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81401871, 81401162, 81572227, 81501907, 81371988]; Zhejiang Provincial Natural Science Foundation of ChinaNatural Science Foundation of Zhejiang Province [LY15H060008, LY14H170002]; Zhejiang Medical Science Foundation [2013KYA127, 2013KYB177]; Wenzhou Science and Technology Bereau Foundation [S20100048, Y20100357]; Zhejiang Provincial Traditional Chinese Medicine Technology Project [2016ZA141]; Zhejiang Provincial Medical and Health Technology Project [2016KYA138]
出版者	NATURE PUBLISHING GROUP
出版地	LONDON
ISSN	2041-4889
卷号	7 期号:10 页码:e2441.
DOI	10.1038/cddis.2016.334
页数	13
WOS类目	Cell Biology
WOS研究方向	Cell Biology
WOS记录号	WOS:000387358800039
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	27787519
PMC记录号	PMC5133996
SCOPUSEID	2-s2.0-85018468226
通讯作者地址	[Xu, Huazi]Department of Orthopaedics,The Second Affiliated Hospital,Wenzhou Medical University,NO.109, XueYuan Road (West), LuCheng District,Wenzhou,325000,China
Scopus学科分类	Immunology;Cellular and Molecular Neuroscience;Cell Biology;Cancer Research
TOP期刊	TOP期刊
引用统计	被引频次：188[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/6938
专题	第二临床医学院，附属第二医院、育英儿童医院附属第二医院
通讯作者	Xu, Huazi
作者单位	1.Department of Orthopaedics,The Second Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 2.Zhejiang Provincial Key Laboratory of Orthopaedics,Wenzhou,China; 3.Department of Spinal Surgery,Shanghai East Hospital,Tongji University School of Medicine,Shanghai,China; 4.Chinese Orthopaedic Regenerative Medicine Society,Hangzhou,China
第一作者单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院
通讯作者单位	附属第二医院
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院
推荐引用方式 GB/T 7714	Chen, Deheng,Xia, Dongdong,Pan, Zongyou,et al. Metformin protects against apoptosis and senescence in nucleus pulposus cells and ameliorates disc degeneration in vivo[J]. CELL DEATH & DISEASE,2016,7(10):e2441..
APA	Chen, Deheng., Xia, Dongdong., Pan, Zongyou., Xu, Daoliang., Zhou, Yifei., ... & Tian, Naifeng. (2016). Metformin protects against apoptosis and senescence in nucleus pulposus cells and ameliorates disc degeneration in vivo. CELL DEATH & DISEASE, 7(10), e2441..
MLA	Chen, Deheng,et al."Metformin protects against apoptosis and senescence in nucleus pulposus cells and ameliorates disc degeneration in vivo".CELL DEATH & DISEASE 7.10(2016):e2441..