Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusion <p>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.</p>

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

  • Zeyu Yang,
  • Lin Li,
  • Rubing Lin,
  • Meini Cen

摘要

Background

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.

Methods

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.

Results

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.

Conclusion

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.