title: Chromatin remodeling enzyme CHD7 is necessary for osteogenesis of human mesenchymal stem cells.
abstract: 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.
authors: State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, 610041, China.
authors: Yi
authors: Y
authors: Chen
authors: State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, 610041, China.
authors: Mengyuan
authors: M
authors: Wang
authors: Division of Oral Biology and Medicine, School of Dentistry, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
authors: Demeng
authors: D
authors: Chen
authors: State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, 610041, China; Department of Orthodontics, West China School of Stomatology, Sichuan University, Chengdu, 610041, China. Electronic address: wangjunv@scu.edu.cn.
authors: Jun
authors: J
authors: Wang
authors: State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, 610041, China; Dental Implant Center, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China. Electronic address: ningakang20088@163.com.
authors: Ning
authors: N
authors: Kang
mesh_terms: D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics; D011485:Protein Binding; D051898:Smad1 Protein / Q000378:metabolism; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D051898:Smad1 Protein; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D004265:DNA Helicases; C491434:CHD7 protein, human
keywords: CHD7; Enhancer; MSC; Osteogenesis; SMAD1