Open AccessMetformin protects against apoptosis and senescence in nucleus pulposus cells and ameliorates disc degeneration in vivo
Author(s) -
Deheng Chen,
Dongdong Xia,
Zongyou Pan,
Dan Xu,
Yifei Zhou,
Yaosen Wu,
Ningyu Cai,
Qian Tang,
Chenggui Wang,
Meijun Yan,
Jing Jie Zhang,
Kailiang Zhou,
Quan Wang,
Yong Feng,
Xiangyang Wang,
Huazi Xu,
Xiaolei Zhang,
Naifeng Tian
Publication year - 2016
Publication title -
cell death and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.482
H-Index - 111
ISSN - 2041-4889
DOI - 10.1038/cddis.2016.334
Subject(s) - autophagy , metformin , apoptosis , senescence , in vivo , microbiology and biotechnology , chemistry , biology , endocrinology , biochemistry , diabetes mellitus
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.