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

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.

Systematic Elaboration of the Pharmacological Targets and Potential Mechanisms of ZhiKe GanCao Decoction for Preventing and Delaying Intervertebral Disc Degeneration

“…On the other hand, endoplasmic reticulum (ER) stress and ECM degradation are important factors in the development of IDD. Autophagy can effectively repair ER stress and maintain ECM homeostasis [41]. Moreover, TP53 and CASP3, among the key targets, are mainly associated with induction of apoptosis and senescence, which further confirmed the potential of ZKGCD in treating IDD.…”

BMP7 ameliorates intervertebral disc degeneration in type 1 diabetic rats by inhibiting pyroptosis of nucleus pulposus cells and NLRP3 inflammasome activity

“…1 D) displayed marked demarcation between NP tissues and annulus fibrosus (AF) tissues with abundant proteoglycans and glycosaminoglycans in normal rats, while STZ-induced T1DM rats exhibited blurred demarcation between NP tissues and AF tissues with loss of proteoglycans and glycosaminoglycans. ECM degradation represents an important marker of IDD (Lin et al 2021 ), and ECM-related genes were further detected. IHC results (Fig.…”

Endoplasmic reticulum stress associates with the development of intervertebral disc degeneration

“…Zhen Lin et al. reports that eicosapentaenoic acid can inhibit the mRNA and protein expression of ERS markers, such as GRP78, ATF4, and CHOP, and promote the synthesis of ECM components collagen II and aggrecan, indicating potential crosstalk between ERS and ECM metabolism in IDD ( 73 ). Previous studies identify that AGEs accumulation in IVD acts as an essential risk factor associating with cell apoptosis and impeding ECM metabolism via ERS ( 74 ).…”