MiR-194 regulates chondrogenic differentiation of human adipose-derived stem cells by targeting Sox5.

Osteoarthritis, also known as degenerative arthritis or degenerative joint disease, causes pain and disability worldwide. Cartilage regeneration is key to finding a cure for this disease. Adipose-derived stem cells (ASCs) are capable of differentiating into cartilage lineages in vitro and they have shown promise in the field of regenerative medicine. However, the underlying mechanisms remain unclear. In this study, we demonstrated that miR-194 levels gradually decreased during the chondrogenic differentiation of human ASCs (hASCs). After predicting the target of miR-194 using Pictar and Targetscan, we hypothesized that Sox5 is potentially the key link between miR-194 and the chondrogenesis of ASCs. Initially, we demonstrated that Sox5 is a target of miR194 according to luciferase assay analysis. We further demonstrated that the differentiation of ASCs can be controlled by miR-194 through gain or loss of function experiments, and we observed that the down-regulation of miR-194 increases its direct target gene, Sox5, and results in enhanced chondrogenic differentiation of hASCs, whereas up-regulation decreases Sox5 and inhibits chondrogenesis. We also found that miR-194 correlates with Sox5 in osteoarthritis. These findings, taken together, are the first to illustrate the critical role of miR-194 in hASC chondrogenesis, and may provide novel insight beneficial to cell manipulation methods during cartilage regeneration.

骨关节炎，也称为退行性关节炎或退行性关节病，在全球范围内导致疼痛和残疾。软骨再生是找到这种疾病治愈方法的关键。脂肪来源干细胞（ASCs）能够在体外分化为软骨谱系，并且它们在再生医学领域已显示出前景。然而，潜在机制仍不清楚。在这项研究中，我们证明在人脂肪来源干细胞（hASCs）的软骨形成分化过程中，miR - 194水平逐渐降低。在使用Pictar和Targetscan预测miR - 194的靶标后，我们假设Sox5可能是miR - 194与ASCs软骨形成之间的关键联系。首先，根据荧光素酶检测分析，我们证明Sox5是miR - 194的一个靶标。我们通过功能获得或丧失实验进一步证明，miR - 194能够控制ASCs的分化，并且我们观察到miR - 194的下调会增加其直接靶基因Sox5，从而导致hASCs的软骨形成分化增强，而上调则会降低Sox5并抑制软骨形成。我们还发现miR - 194在骨关节炎中与Sox5相关。综上所述，这些发现首次阐明了miR - 194在hASC软骨形成中的关键作用，并可能为软骨再生过程中的细胞操作方法提供有益的新见解。