MiR-24-3p induces human intervertebral disc degeneration by targeting insulin-like growth factor binding protein 5 and the ERK signaling pathway

Abstract

AimsIntervertebral disc degeneration (IDD) was associated with microRNA (miRNA) dysregulation. Therefore, we verified the hypothesis that miRNAs modulated IDD by affecting the insulin-like growth factor-binding protein 5 (IGFBP5)/extracellular signal-regulated kinase (ERK) signaling pathway. Materials and methodsThe miRNA expression profiles in nucleus pulposus (NP) cells were compared between patients with IDD and controls, and miRNA microarray and quantitative real-time PCR (RT-qPCR) assays were utilized. Luciferase reporter and Western blotting assays were performed to detect the miRNA targets. Key findingsRT-qPCR confirmed that the expression level of miR-24-3p was significantly increased in degenerative NP cells. Moreover, the miR-24-3p level was positively correlated with the disc degeneration grade, and miR-24-3p significantly induced NP cell apoptosis. IGFBP5 was determined as a target of miR-24-3p, and IGFBP5 knockdown induced effects on NP cells similar to those induced by miR-24-3p. Compared with control cells, NP cells presented with miR-24-3p overexpression or IGFBP5 downregulation via shRNAs had significantly increased p-ERK and Bax expression levels. Furthermore, in vivo analysis on IDD rat model showed that the downregulation of miR-24-3p could effectively suspend IDD. SignificanceThese results demonstrated that miR-24-3p upregulation could promote IDD through IGFBP5 and the ERK signaling pathway.