MiR-199a-3p mediates the adipogenic differentiation of bone marrow-derived mesenchymal stem cells by regulating KDM6A/WNT signaling

Abstract

A number of evidences suggest that microRNAs are involved in the adipogenic commitment of mesenchymal stem cells (MSCs). Recent studies have investigated that miR-199a-3p played a pivotal role in adipocyte differentiation. However, the detailed mechanism in this complex biological process remains largely unknown. In current study, we found that the expression of miR-199a-3p was gradually increased during adipogenic differentiation of bone marrow derived mesenchymal stem cells (BMMSCs). Enhanced expression of miR-199a-3p promoted adipogenesis, whereas silence of miR-199a-3p rescued BMMSCs from adipogenic commitment. For further mechanism exploration, KDM6A was confirmed to be the target of miR-199a-3p and the expression of KDM6A was gradually decreased during adipogenic differentiation of BMMSCs. Furthermore, up-regulation of KDM6A markedly abolished the miR-199a-3p overexpression induced adipogenic augmentation, whereas down-regulation of KDM6A suppressed the adipogenic reduction caused by miR-199a-3p silence. In addition, WNT signaling was also verified to be the downstream of miR-199a-3p/KDM6A to regulate adipogenic differentiation of BMMSCs. Taken together, current results indicate that miR-199a-3p regulate adipogenesis of BMMSCs by targeting KDM6A/WNT signaling, which highlights a new insight for a better understanding of molecular mechanism and stem cell based therapy on osteoporotic diseases.

Keywords: Adipogenic differentiation; KDM6A; WNT signaling; miR-199a-3p.