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Research Paper|Volume 11, Issue 16|pp 6014—6028

MiR-146b accelerates osteoarthritis progression by targeting alpha-2-macroglobulin

Xin Liu1,2, Liangliang Liu1,2, Hongbo Zhang1,2, Yan Shao1,2, Ziyu Chen1,2, Xiaofeng Feng1,2, Hang Fang1,2, Chang Zhao1,2, Jianying Pan1,2, Haiyan Zhang1,2, Chun Zeng1,2, Daozhang Cai1,2
  • 1Department of Orthopedics, Academy of Orthopaedics, Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China
  • 2Orthopaedic Hospital of Guangdong Province, Guangzhou 510630, China
Received: February 14, 2019Accepted: August 5, 2019Published: August 17, 2019
https://doi.org/10.18632/aging.102160

Copyright © 2019 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY 3.0) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Osteoarthritis (OA) is an aging-related chronic degenerative disease characterized by the degradation of chondrocyte extracellular matrix (ECM). Previous studies have suggested that microRNAs (miRNAs) are associated with OA, but the role of miR-146b in OA remains unclear. The aim of this study was to determine the role of miR-146b in OA progression. The effect of miR-146b on ECM degradation were studied in mouse chondrocytes transfected with miRNA and treated with IL-1β. Cell viability and the expression levels of proteolytic enzymes in the transfected cells were assessed by real-time RT-PCR, ELISA and Western blots. We found downregulation of miR-146b expression in chondrocytes dramatically inhibited IL-1β-induced caspase activation and proteolytic enzyme expression via influencing its targeted Alpha-2-macroglobulin (A2M). Luciferase reporter assays confirmed that A2M mRNA was negatively regulated by miR-146b in chondrocytes. Intra-articular injection of antago-miR-146b against miR-146b effectively protected mice from the progression of DMM-induced osteoarthritis by inhibiting cartilage proteoglycan degradation. Our study indicates that miR-146b plays a critical role in the progression of injury-induced osteoarthritis by directly targeting A2M expression to elevate the proteolytic enzyme production and stimulate chondrocytes apoptosis, and miR-146b as well as A2M could be therapeutic targets.