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

Abstract

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.