Autophagy Is a Protective Response to the Oxidative Damage to Endplate Chondrocytes in Intervertebral Disc: Implications for the Treatment of Degenerative Lumbar Disc.

Ke Chen,Fei Yu,Jianjing Lin,Junxuan Ma,Deming Xiao,Xiaohua Lv,Wei Li

doi:10.1155/2017/4041768

Abstract

Low back pain (LBP) is the leading cause of disability in the elderly. Intervertebral disc degeneration (IDD) was considered as the main cause for LBP. Degeneration of cartilaginous endplate was a crucial harmful factor during the initiation and development of IDD. Oxidative stress was implicated in IDD. However, the underlying molecular mechanism for the degeneration of cartilaginous endplate remains elusive. Herein, we found that oxidative stress could induce apoptosis and autophagy in endplate chondrocytes evidenced by western blot analysis, flow cytometry, immunofluorescence staining, GFP-LC3B transfection, and MDC staining. In addition, we also found that the apoptosis of endplate chondrocytes was significantly increased after the inhibition of autophagy by bafilomycin A1 shown by flow cytometry. Furthermore, mTOR pathway upstream autophagy was greatly suppressed suggested by western blot assay. In conclusion, our study strongly revealed that oxidative stress could increase autophagy and apoptosis of endplate chondrocytes in intervertebral disc. The increase of autophagy activity could prevent endplate chondrocytes from apoptosis. The autophagy in endplate chondrocytes induced by oxidative stress was mTOR dependent. These findings might shed some new lights on the mechanism for IDD and provide new strategies for the treatments of IDD.

Highlights

Low back pain (LBP) is the leading cause of disability in the elderly, resulting in low quality of life and high economic burden [1, 2]
To further corroborate these findings, immunofluorescence staining for type II collagen was carried out, and the data showed that type II collagen was distributed in the cytoplasm (Figure 1(c))
To investigate the apoptosis response of endplate chondrocytes treated by oxidative stress, the protein expression of Bax and Bcl-2 was determined by western blot

Summary

Introduction

Low back pain (LBP) is the leading cause of disability in the elderly, resulting in low quality of life and high economic burden [1, 2]. Intervertebral disc degeneration (IDD) was considered as the main cause for LBP [4, 5]. Autophagy was detected in endplate chondrocytes of intervertebral disc and proved to be implicated in the degeneration of cartilaginous endplate [24, 25]. Oxidative stress, resulting from overproduction of reactive oxygen species (ROS), was implicated in IDD by inducing premature senescence, promoting catabolic metabolism, and causing the apoptosis of intervertebral disc cells [26,27,28,29]. No study was designed to explore the autophagy and apoptosis of cartilaginous endplate under oxidative stress. We hypothesize that autophagy is a protective response to the oxidative damage to endplate chondrocytes in intervertebral disc. The change of autophagy and apoptosis of endplate chondrocytes together with the crosstalk between them was investigated

Materials and Methods

Results

Discussion