Eicosapentaenoic Acid-Induced Autophagy Attenuates Intervertebral Disc Degeneration by Suppressing Endoplasmic Reticulum Stress, Extracellular Matrix Degradation, and Apoptosis.

Zhen Lin,Zhongke Lin,Libin Ni,Long Wu,Zhao Zhang,Yu Jin,Xinlei Lu,Cheng Teng

doi:10.3389/fcell.2021.745621

Abstract

Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP), but there is still a lack of effective therapy. Multiple studies have reported that endoplasmic reticulum (ER) stress and extracellular matrix (ECM) degradation exert an enormous function on the occurrence and development of IDD. Autophagy can effectively repair ER stress and maintain ECM homeostasis. Eicosapentaenoic acid (EPA) can specifically induce autophagy. The purpose of this study is to demonstrate that EPA can promote autophagy, reduce ECM degradation and ER stress in vitro, thereby reducing cell apoptosis, and the protective effects of EPA in an IDD-rat model in vivo. Western blot and immunofluorescence were used to detect the autophagic flux, ER stress, ECM degradation, and apoptosis in nucleus pulposus cells (NPCs) treated by EPA. We also used puncture-induced IDD rats as experimental subjects to observe the therapeutic effect of EPA on IDD. Our findings indicated that EPA can effectively improve the autophagy activity in NPCs, inhibit the endoplasmic reticulum stress process, reduce the degree of cell apoptosis, and exert protective effects on the anabolism and catabolism of ECM. In addition, in vivo investigations demonstrated that EPA ameliorated the progression of puncture-induced IDD in rats. In conclusion, this study revealed the intrinsic mechanisms of EPA’s protective role in NPCs and its potential therapeutic significance for the treatment of IDD.

Highlights

Low back pain (LBP) affects up to 80% of adults in a certain period of life and is the leading cause of disability Global (2016), it may cause a massive economic burden both on the individuals and society (Smith et al, 2014)
The results revealed that Eicosapentaenoic acid (EPA) did not have a significant impact on the cell viability of nucleus pulposus cells (NPCs) if the EPA concentration was lower than 50 μM
EdU staining results suggested that the proliferation of NPCs was decreased after tert-butyl hydroperoxide (TBHP) treatment; EPA remarkably increased the ratio of proliferating cells in TBHP-treated NPCs (Figures 1D,E)

Summary

Introduction

Low back pain (LBP) affects up to 80% of adults in a certain period of life and is the leading cause of disability Global (2016), it may cause a massive economic burden both on the individuals and society (Smith et al, 2014). It can be seen that LBP has imposed a huge social and economic burden on our humanity (Dagenais et al, 2008). Intervertebral disc degeneration (IDD) is a major cause of LBP (Wáng et al, 2016; Wiet et al, 2017; Millecamps and Stone, 2018). The normal human intervertebral disc is a fibrocartilaginous structure that consists of the three following parts: 1) the outer annulus fibrosus (AF) composed of fibroblast-like cells and type I Collagen; 2) the inner soft nucleus pulposus (NP) composed of chondrocyte-like cells (or notochordal cells in a foetus) (Bach et al, 2015; Rodrigues-Pinto et al, 2016), proteoglycan, and water; and 3) cartilage endplates (Liu et al, 2018). Quite a few potential drug targets that have the opportunity to be used for clinical treatment of diseases are continuously being discovered in this field (Xu et al, 2020; Yarmohammadi et al, 2020)

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