MicroRNA‐181a exerts anti‐inflammatory effects via inhibition of the ERK pathway in mice with intervertebral disc degeneration

Abstract

Enzymatic decomposition of extracellular matrix and possibly local inflammation may cause intervertebral disc degeneration (IDD). MicroRNAs have been reported to correlate with the development of IDD. In this experiment, we aim at finding out the role of miR-181a in the inflammation of IDD and the underlying mechanism. The targeting relationship between miR-181a and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was verified. Following the establishment of IDD mouse models, disc height index (DHI) and the change of DHI (%DHI) were measured.The functional role of miR-181a in IDD was determined using ectopic expression and depletion and reporter assay experiments. Expression of miR-181a, TRAIL, extracellular signal-regulated kinase (ERK) pathway-related genes and inflammatory factors was evaluated. Also, the expression of collagen I and collagen II was observed. miR-181a directly targeted TRAIL. IDD mice exhibited significant degeneration of the intervertebral disc. miR-181a was downregulated while TRAIL was upregulated in mice with IDD. miR-181a upregulation and the ERK pathway inhibition could reduce expression of TRAIL, ERK pathway-related genes, inflammatory factors, and collagen I, but promote collagen II expression. Our results reveal that upregulation of miR-181a protects against inflammatory response by inactivating the ERK pathway via suppression of TRAIL in IDD mice. These results point to miR-181a as a potential therapeutic target for the clinical management of IDD. K E Y W O R D SERK pathway, inflammation, intervertebral disc degeneration, microRNA-181a, TRAIL

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

“…At week 8 after the operation, the intervertebral disc tissues were collected for histological evaluation. 16,17…”

“…At week 8 after the operation, the intervertebral disc tissues were collected for histological evaluation. 16,17 Isolation and culture of nucleus pulposus cells Whole lumbar spines of rats were collected, the ligaments adjacent to the intervertebral disc and the attached muscles were cleared, and the nucleus pulposus tissues from the lumbar intervertebral discs were carefully collected using scalpel blades and curettes. Next, the collected nucleus pulposus tissues were cut into 1 mm 3 tissue blocks.…”

MicroRNA Expression Profile in Peripheral Blood Lymphocytes of Sheep Vaccinated with Nigeria 75/1 Peste Des Petits Ruminants Virus

“…The miR-181a also has been shown to facilitate cardiomyocyte apoptosis by suppressing Bcl-2 expression [66]. Moreover, miR-181a played anti-inflammatory role via repression of the ERK signaling pathway in mice with intervertebral disc degeneration [67]. T cell responses were impaired during HCV infection by miR-181a-mediated expression of DUSP6 which was a marker of T cell aging [68].…”

Identification of Key Genes and Pathways Associated With Pathogenesis of Intervertebral Disc Degeneration by Integrated miRNA-mRNA Network Analysis

“…A preclinical study showed that miR-141 promoted IDD progression by interacting with SIRT1/NF-κB pathway and inhibition of miR-141 in vivo may serve as a potential therapeutic approach in the treatment of IDD [21] . miR-181a-5p was downregulated in IDD mice while upregulation of miR-181a protected against in ammatory response by inactivating the ERK pathway via suppression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in IDD mice [22] . This result is consistent with nding of our miRNA-miRNA network.…”