近年来,MicroRNAs(miRs)在骨关节炎(OA)发病机制中受到广泛关注,我们之前的研究证实,miR-140-5p的关节内注射(IAJ)可缓解大鼠早期OA(EOA)的进展.本研究旨在探讨miR-140-5p的单个IAJ(SIAJ)对不同阶段OA的治疗作用和miR-140-5p的多个IAJ(MIAJ)对EOA的治疗作用及其可能机制。首先,手术诱导大鼠OA模型,九例在手术后一周用Cy5-miR-140-5p的IAJ治疗,并分析了不同时间的荧光分布。然后,72只大鼠在手术后一周用miR-140-5p的SIAJ或miR-140-5p的MIAJ治疗不同阶段,在不同时间对OA进展进行宏观和组织学评估。最后,miR-140-5p的下游靶标和潜在分子机制通过生物信息学预测并部分验证.因此,关节内注射的miR-140-5p进入软骨,可被软骨细胞迅速吸收.miR-140-5p的IAJ(s)提高了行为评分,软骨细胞数,软骨厚度,和不同程度的病理评分。具体来说,较早地施用了miR-140-5p的SIAJ,治疗效果越好;同时,miR-140-5p的MIAJ对EOA表现出比SIAJ更好的治疗效果。预测了84个rno-miR-140-5p的潜在靶基因和机制,实验验证了miR-140-5p对潜在靶基因VEGFA和JAG1的影响。总的来说,miR-140-5p的IAJ通过调节大鼠的多种生物学过程和途径有效缓解EOA进展,代表了一种有希望的EOA治疗方法。
MicroRNAs (miRs) receive extensive attention in osteoarthritis (OA) pathogenesis in recent years, and our previous study confirmed that an intra-articular injection (IAJ) of miR-140-5p alleviates early-stage OA (EOA) progression in rats. This study aims to investigate the therapeutic effect and potential mechanisms of single IAJ (SIAJ) of miR-140-5p on different stage OA and multiple IAJs (MIAJ) of miR-140-5p on EOA. Firstly, the OA model was surgically induced in rats, nine were treated with IAJ of Cy5-miR-140-5p at one week after surgery, and fluorescence distribution was analyzed at different times. Then, 72 rats were treated with SIAJ of miR-140-5p at different stages or MIAJ of miR-140-5p at one week after surgery, and OA progression was evaluated macroscopically and histologically at different times. Finally, the downstream targets and underlying molecular mechanisms of miR-140-5p were predicted by bioinformatics and partially validated. As a result, the intra-articularly injected miR-140-5p entered cartilage and could be taken up by chondrocytes rapidly. IAJ(s) of miR-140-5p improved the behavioral scores, chondrocyte number, cartilage thickness, and pathological scores to varying degrees. Specifically, the earlier a SIAJ of miR-140-5p was administrated, the better the therapeutic effect; meanwhile, MIAJ of miR-140-5p exhibited a better therapeutic effect than SIAJ on EOA. Eighty-four potential target genes and mechanisms of rno-miR-140-5p were predicted, and the effect of miR-140-5p on the potential target genes VEGFA and JAG1 was experimentally validated. Collectively, IAJs of miR-140-5p effectively alleviate EOA progression by modulating multiple biological processes and pathways in rats, representing a promising therapeutic for EOA.