Eicosapentaenoic Acid-Induced Autophagy Attenuates Intervertebral Disc Degeneration by Suppressing Endoplasmic Reticulum Stress, Extracellular Matrix Degradation and Apoptosis: An in vivo and in vitro Experiment

Background: Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP), and effective therapies are still lacking. Many previous studies have shown that endoplasmic reticulum stress (ER-stress) and extracellular matrix (ECM) degradation play an important role in the development of IDD. Autophagy can effectively repair endoplasmic reticulum stress and maintain ECM homeostasis. Eicosapentaenoic Acid (EPA) can specifically induce autophagy. Methods: Western blotting, immunofluorescence staining, and confocal microscope assay were applied to demonstrate the molecular mechanism of EPA in the nucleus pulposus cells (NPCs) in vitro. The therapeutic potential of EPA was investigated using puncture-induced rat models in vivo. Findings: EPA can effectively activate the autophagy intensity in NPCs, inhibit the progress of ER-stress, and reduce the degree of apoptosis and made the protective effects on the anabolism and catabolism of ECM. Further in vivo investigation demonstrated that EPA ameliorated the progression of puncture-induced IDD in rats. Interpretation: This finding reveals the intrinsic mechanism of EPA's protective role in NPCs and its potential therapeutic value in the treatment of IDD. Funding: This study is funded by Wenzhou Science and Technology Bureau Foundation (20180031). Declaration of Interest: None to declare. Ethical Approval: The animal use and care protocols were strictly adhered to according to the guidelines approved by Wenzhou Medical University Animal Care and Use Committee.