Tissue Renin-Angiotensin System (tRAS) Induce Intervertebral Disc Degeneration by Activating Oxidative Stress and Inflammatory Reaction.

Kaiqiang Sun,Yan Jiang,Fudong Li,Jian Zhu,Fanqi Kong,Xiaofei Sun,Lu Gao,Le Huan,Weiguo Zou,Jingchuan Sun,Yuan Wang,Ximing Xu,Feng Lin,Bing Zheng,Jiangang Shi,Sidong Yang

doi:10.1155/2021/3225439

Abstract

Lumbar intervertebral disc degeneration (IDD) has been the major contributor to low back pain (LBP). IDD is an chronic inflammation process, with the activation of plentiful inflammation-related cytokines and ECM degradation-related enzymes. In the past few years, hypertension has been reported to correlate with LBP. In addition, the local tissue renin-angiotensin system (tRAS) has been identified in multiple tissues, including the spinal cord, skin, kidney, heart, and bone. Recently, tRAS has also been established in both bovine and human intervertebral disc tissues, especially in the degenerated disc tissue. However, the exact of tRAS and IDD remains unknown. In this present study, proteomic analysis, molecular biology analysis, and animal model were all used. Firstly, we revealed that tRAS was excessively activated in the human degenerated intervertebral disc tissue via proteomic analysis and molecular biology analysis. Then, in vitro experiment suggested that Ang II could decrease the cell viability of human NP cells and promote NP cell apoptosis, senescence, oxidative stress, and NLRP3 activation in human NP cells. In addition, Ang II could also trigger degeneration and fibrosis phenotype in human NP cells. Finally, the animal model demonstrated that the local activated ACE/Ang II axis in the NP tissue could accelerate IDD in aging spontaneously hypertensive rats (SHR). Collectively, the degenerated intervertebral disc tissue showed excessively activated tRAS, and local activated tRAS could induce NP cell senescence, apoptosis, oxidative stress, and inflammatory reaction to promote IDD. These biological effects of Ang II on human NP cells may provide novel insight into further treatment of IDD.

Highlights

Low back pain (LBP) has been the major contributor to hospitalization in patients with degenerative lumbar diseases, which brings enormous social and economic burdens for patients and their families worldwide [1]
During the process of intervertebral disc degeneration (IDD), various pathological changes occur in the microenvironment of the nucleus pulposus tissue (NP) tissue, such as cell apoptosis, cell senescence, inflammatory reaction, and oxidative stress, which will result in increased catabolic reaction and decreased synthetic reaction [4]
AGT (P01019), the origin of Ang II, was found to be expressed higher in severely degenerated group, indicating increased activation of tissue renin-angiotensin system (tRAS) that may correlate with IDD

Summary

Introduction

Low back pain (LBP) has been the major contributor to hospitalization in patients with degenerative lumbar diseases, which brings enormous social and economic burdens for patients and their families worldwide [1]. Of the massive pathogenic factors, lumbar intervertebral disc degeneration (IDD) has been the mostly studied. During the process of IDD, various pathological changes occur in the microenvironment of the NP tissue, such as cell apoptosis, cell senescence, inflammatory reaction, and oxidative stress, which will result in increased catabolic reaction and decreased synthetic reaction [4]. These abnormal biological processes will cause IDDrelated diseases, such as spinal canal stenosis, adjacent segment degeneration (ASD), and spinal instability [4]

Methods

Results

Conclusion