Overexpression of microRNA-185 alleviates intervertebral disc degeneration through inactivation of the Wnt/β-catenin signaling pathway and downregulation of Galectin-3.

Abstract

BackgroundRecent studies have found that microRNAs (miRNAs) play a critical role in development and progression of intervertebral disc degeneration. In the present study, we examined the role of miR-185 in nucleus pulposus cell behavior in vitro and the histological changes of intervertebral disc tissue in intervertebral disc degeneration rat models in vivo.MethodsIntervertebral disc degeneration models were developed in Sprague-Dawley rats. Intervertebral disc tissue was collected for histological evaluation after miR-185 agomir/agomir transduction. Next, nucleus pulposus tissues were collected from lumbar intervertebral discs to isolate nucleus pulposus cells, which were treated with miR-185 mimic/inhibitor and an inhibitor of the Wnt signaling pathway to assess cell viability and apoptosis.ResultsWe observed a high expression of Galectin-3 in nucleus pulposus cells of rats with intervertebral disc degeneration. Bioinformatics prediction and dual-luciferase reporter assay confirmed that miR-185 specifically binds to and negatively regulates Galectin-3. Furthermore, we found that miR-185 inhibition resulted in increased expression of Galectin-3, pro-autophagy factors (LC3 and Beclin-1), and pro-apoptosis factors (caspase-3 and Bax), along with the activation of the Wnt/β-catenin signaling pathway. Moreover, the gain- and loss-of-function studies suggested that miR-185 overexpression promoted cell viability and inhibited nucleus pulposus cell apoptosis and autophagy via inactivation of the Wnt/β-catenin signaling pathway. Moreover, miR-185 agomir alleviated the histological changes observed in intervertebral disc tissues in intervertebral disc degeneration rats, which helped us validate the results observed in vitro.ConclusionsOverexpression of miR-185 promotes nucleus pulposus cell viability and reduces the histological changes observed in intervertebral disc tissues in rats with intervertebral disc degeneration via inactivation of the Wnt/β-catenin signaling pathway and Galectin-3 inhibition. Our findings also highlight the potential of miR-185 as a promising novel therapeutic target to prevent and control intervertebral disc degeneration.