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

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.

• Authors: Kaiqiang Sun, Xiaofei Sun, Jingchuan Sun, Yan Jiang, Feng Lin, Fanqi Kong, Fudong Li, Jian Zhu, Le Huan, Bing Zheng, Yuan Wang, Weiguo Zou, Lu Gao, Ximing Xu, Jiangang Shi
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2021 Pg. 3225439 ( 2021) ISSN: 1942-0994 [Electronic] United States
• PMID: 34413926 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Kaiqiang Sun et al.

Topics

• Adult
• Aged
• Animals
• Apoptosis
• Cell Proliferation
• Cells, Cultured
• Humans
• Inflammation (complications, metabolism, pathology)
• Intervertebral Disc (metabolism, pathology)
• Intervertebral Disc Degeneration (etiology, metabolism, pathology)
• Male
• Middle Aged
• Nucleus Pulposus (metabolism, pathology)
• Oxidative Stress
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Renin-Angiotensin System
• Young Adult