Mesenchymal stem cells (MSCs) have great therapeutic potential due to their abilities to self-renewal and their potential for differentiating into a variety of cell lineages. However, how to improve the differentiation efficiency of MSC into osteoblast remains a big challenge in the field of bone regenerative medicine. In current study, we identified a role of CHD7 in osteogenic differentiation of MSC. We showed that CHD7 expression in MSC could be induced by BMP2 or osteogenic induction medium. Depletion of CHD7 in MSC via siRNA knockdown resulted in inhibition of key osteogenic transcription factors and impaired osteogenic capability of MSC. Complementarily, overexpression of CHD7 in MSC led to increased osteogenic ability. Mechanistically, we demonstrated that CHD7 interacted with SMAD1, downstream factor of BMP signaling. BMP2 stimulated the binding of CHD7 to the enhancer region of SP7. Finally, CHD7-silencing MSC showed comprised osteogenic ability when cultured with scaffold in vivo. Overall, our study established a new epigenetic regulation of MSC osteogenic differentiation and provided a potential target for controlling MSC osteogenesis. (C) 2016 Elsevier Inc. All rights reserved.