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

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 . 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 . 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.