MicroRNA‐181a exerts anti‐inflammatory effects via inhibition of the ERK pathway in mice with intervertebral disc degeneration. Issue 3 (11th September 2019)

• Record Type: Journal Article
• Authors: Sun, Yanpeng; Shi, Xiangqin; Peng, Xiaodong; Li, Yanzhou; Ma, Husheng; Li, Dongfang; Cao, Xiangyang
• Is Part Of: Journal of cellular physiology. Volume 235:Issue 3(2020:Mar.)
• Page Start: 2676
• Page End: 2686
• Publication Date: 2019-09-11
• Subjects: ERK pathway -- inflammation -- intervertebral disc degeneration -- microRNA‐181a -- TRAIL; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.29171
• Languages: English
• ISSNs: 0021-9541

Abstract

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.