MicroRNA-137 inhibits the inflammatory response and extracellular matrix degradation in lipopolysaccharide-stimulated human nucleus pulposus cells by targeting activin a receptor type I

This study aimed to investigate the role played by microRNA (miR)-137 in intervertebral disc degeneration via targeting activin A receptor type I (ACVR1) and the underlying mechanism. Human nucleus pulposus cells were exposed to 10 ng/mL lipopolysaccharide (LPS) to establish an in vitro intervertebral disc degeneration model. ACVR1, extracellular matrix degradation-associated genes (aggrecan and collagen type II) and miR-137 levels were assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting assays. The MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay and flow cytometry were used to evaluate nucleus pulposus cell viability and apoptosis. Additionally, the association between miR-137 and ACVR1 was predicted and verified using bioinformatic software and dual-luciferase reporter assays. Furthermore, the secretion of inflammatory factors was analyzed via enzyme linked immunosorbent assay (ELISA). Our results confirmed that ACVR1 was upregulated in lipopolysaccharide-treated nucleus pulposus cells. Lipopolysaccharide suppressed cell viability, promoted apoptosis, enhanced the secretion of inflammatory factors, and reduced aggrecan and collagen type II expression. However, these results were reversed upon ACVR1 silencing. Our data revealed that ACVR1 directly targets miR-137 and is negatively regulated by miR-137 in nucleus pulposus cells. Additionally, the miR-137 mimic promoted cell growth, reduced cell apoptosis, reduced the secretion of inflammatory cytokines, and accelerated extracellular matrix accumulation in lipopolysaccharide-exposed nucleus pulposus cells. However, ACVR1 plasmid abolished the functions of the miR-137 mimic in lipopolysaccharide-exposed nucleus pulposus cells. Together, these findings indicate that miR-137 suppresses the inflammatory response and extracellular matrix degradation in lipopolysaccharide-treated nucleus pulposus cells by targeting ACVR1.