Metformin Protects Against Apoptosis and Senescence in Nucleus Pulposus Cells and Ameliorates Disc Degeneration in Vivo

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2016 Oct 28

PMID 27787519

Citations 160

Authors

Deheng Chen

Dongdong Xia

Zongyou Pan

Daoliang Xu

Yifei Zhou

Yaosen Wu

Ningyu Cai

Qian Tang

Chenggui Wang

Meijun Yan

Jing Jie Zhang

Kailiang Zhou

Quan Wang

Yongzeng Feng

Xiangyang Wang

Huazi Xu

Xiaolei Zhang

Naifeng Tian

Affiliations

Soon will be listed here.

Abstract

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.

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