miR-191-5p attenuates TNF-α-induced inflammation in nucleus pulposus cells via targeting EGR1.

Abstract

Intervertebral disc degeneration (IVDD) is an orthopedic degenerative disease characterized by low back pain, the pathogenesis of which remains inadequately understood. Recent research has illuminated a potential link between dysregulation of microRNAs (miRNAs) and the development of IVDD. The study aimed to elucidate the molecular mechanism by which miR-191-5p affects IVDD. TNF-α was applied to construct cell models of IVDD. RT-qPCR was utilized to detect the content of miR-191-5p, EGR1 and extracellular matrix (ECM) markers. Dual-luciferase reporter assays were conducted to validate the target relationship. CCK-8 and Transwell assays were employed to measure cell viability and migration rates. ELISA was adopted to detect the concentration of inflammatory factors. The content of miR-191-5p was significantly reduced in the nucleus pulposus (NP) of patients with IVDD. And the higher the degree of the intervertebral disc (IVD) degeneration, the lower the content of miR-191-5p in NP. In vitro, miR-191-5p mimic promoted Collagen II expression while suppressing MMP-13 and MMP-3 expression. This effect was abolished by upregulation of EGR1. Furthermore, overexpression of miR-191-5p promoted cell viability and migration while inhibiting apoptosis and secretion of inflammatory cytokines (IL-1β and IL-18), which was eliminated by upregulated EGR1. miR-191-5p enhanced cell viability and migration while concurrently suppressing ECM degradation, apoptosis and inflammatory responses via negative regulation of EGR1, which in turn inhibited the progression of IVDD.