Therapeutic effect and mechanisms of intra-articular injections of microRNA-140-5p on early-stage osteoarthritis in rats

Abstract

Background MicroRNAs (miRs) have received extensive attention in osteoarthritis (OA) pathogenesis in recent years, and our previous study have confirmed that single intra-articular injection (IAJ) of miR-140-5p alleviates early-stage OA (EOA) progression in rats. This study aims to further investigate the effects of single IAJ of miR-140-5p on different stage OA and multiple IAJs of miR-140-5p on EOA, as well as the potential mechanisms. Methods Firstly, OA model was surgically induced in rats, 9 rats were treated with IAJ of Cy5-miR-140-5p at 1 week after surgery, and fluorescence distribution was measured. Then, 72 rats were treated with single IAJ of miR-140-5p at different time after surgery or multiple IAJs of miR-140-5p at 1 week after surgery, and OA progression were evaluated macroscopically and histologically. Finally, bioinformatics analyses were performed and the potential targets and molecular mechanisms of miR-140-5p were predicted. Results Strong fluorescence was observed in the chondrocytes and joint where Cy5-miR-140-5p was injected. Behavioural scores, chondrocyte numbers and cartilage thickness in cartilage were higher, while pathological scores were lower in the miR-140-5p group than in the control group. Specifically, the earlier a single IAJ of miR-140-5p, the better the therapeutic effect, and multiple IAJs exhibited better therapeutic effect than single IAJ on EOA. Bioinformatics analyses predicted 84 potential target genes of rno-miR-140-5p and revealed that these genes enrich in various biological processes and pathways. Conclusions IAJs of miR-140-5p effectively alleviate EOA progression by modulating various biological processes and pathways, and may be a promising therapeutics for EOA.