The Role of miR-31-5p in the Development of Intervertebral Disc Degeneration and Its Therapeutic Potential

Abstract

Intervertebral disc degeneration (IDD) refers to the abnormal response of cell-mediated progressive structural failure. In order to understand the molecular mechanism of the maintenance and destruction of the intervertebral disc, new IDD treatment methods are developed. Here, we first analyzed the key regulators of IDD through microRNAs microarrays. Then, the level of miR-31-5p was evaluated by qRT-PCR. The association between miR-31-5p and Stromal cell-derived factor 1 (SDF-1)/CXCR7 axis was assessed by 3′-untranslated region (UTR) cloning and luciferase assay. The apoptosis of cells under different treatments was evaluated by flow cytometer. The cell proliferation was assessed by EdU assay. After IDD model establishment, the discs of mice tail were harvested for histological and radiographic evaluation in each group. Finally, the protein levels of SDF-1, CXCR7, ADAMTS-5, Col II, Aggrecan, and MMP13 were assessed by western blot. The results show that miR-31-5p is a key regulator of IDD and its level is down-regulated in IDD. Overexpression of miR-31-5p facilitates nucleus pulposus cell proliferation, inhibits apoptosis, facilitates ECM formation, and inhibits the level of matrix degrading enzymes in NP cells. The SDF-1/CXCR7 axis is the direct target of miR-31-5p. miR-31-5p acts on IDD by regulating SDF-1/CXCR7. In vitro experiments further verified that the up-regulation of miR-31-5p prevented the development of IDD. In conclusion, overexpression of miR-31-5p can inhibit IDD by regulating SDF-1/CXCR7.