Downregulation of HMGB1 by miR-103a-3p Promotes Cell Proliferation, Alleviates Apoptosis and in Flammation in a Cell Model of Osteoarthritis.

Abstract

Background: MiR-103a-3p is a small non-coding RNA and has been reported to be involved in osteogenic proliferation and differentiation, but the role of miR-103a-3p in human osteoarthritis (OA) remains unclear.Objectives: In this study, we aimed to explore its function and molecular target in chondrocytes during OA pathogenesis.Materials and Methods: Total 12 experimental OA rat models, together with 12 rats without knee OA lesions were established and cartilage samples were collected. Chondrocytes were treated with LPS in vitro. MiR-103a-3p expression was detected in articular cartilage tissues and chondrocytes using quantitative real-time PCR. Knee OA chondrocytes were transfected with miR-103a-3p mimics, and siHMGB1, respectively. Then cellular proliferation, apoptosis, apoptosis related factors and inflammatory cytokines were analyzed by MTT, flow cytometry, western blot, caspase-3 activity and ELISA, respectively. Potential targets of miR-103a-3p were predicted using series of bioinformatics analysis, then confirmed by luciferase reporter assay.Results: We first found miR-103a-3p was significantly down-regulated in the articular cartilage tissues from experimental OA rats, as well as in chondrocytes treated with LPS in vitro. The gain-of-function assay further demonstrated that up-regulation of miR-103a-3p significantly promoted cell proliferation, inhibited apoptosis and inflammation, which was accompanied with elevated expression of PCNA, and reduced expression of caspase-3, PARP, IL-1β, IL-6, IL-10 and TNF-α. Furthermore, high mobility group box 1 (HMGB1), an important inflammatory mediator of OA, was a target of miR-103a-3p. Moreover, knockdown of HMGB1 mimicked the effects of miR-103a-3p on chondrocytes treated with LPS.Conclusions: Taken together, our study suggests that miR-103a-3p inhibits chondrocyte apoptosis and inflammation in OA, which appears to be an attractive approach to OA treatment.