miR-148a-3p regulates adipocyte and osteoblast differentiation by targeting lysine-specific demethylase 6b

Recent emerging studies of miRNAs in mesenchymal stem cell commitment toward adipocyte and osteoblast provide new insights for the understanding of the molecular basis of adipogenesis and osteogenesis. The current study revealed that miR-148a-3p was altered in primary cultured marrow stromal cells and established stromal ST2 line after adipogenic and/or osteogenic treatment. Supplementing miR-148a-3p activity inhibited cell growth and induced ST2 to differentiate into mature adipocytes. Conversely, inactivation of the endogenous miR-148a-3p suppressed ST2 to fully differentiate. By contrast, supplementation of the miR-148a-3p blunted osteoblast differentiation. Lysine-specific demethylase 6b (Kdm6b), a recently identified regulator of osteoblast differentiation was shown to be a direct target of miR-148a-3p by using the luciferase assay. Overexpression of Kdm6b attenuated miR-148a-3p stimulation of adipogenic differentiation. Taken together, our study provides evidences that miR-148a-3p reciprocally regulates adipocyte and osteoblast differentiation through directly targeting Kdm6b.