Chromatin remodeling enzyme CHD7 is necessary for osteogenesis of human mesenchymal stem cells
Chromatin remodeling enzyme CHD7 is necessary for osteogenesis of human mesenchymal stem cells
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染色质重塑酶CHD7是人间充质干细胞成骨所必需的
DOI：
10.1016/j.bbrc.2016.08.161
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发表时间：
2016-09-30
影响因子：
3.1
通讯作者：
Kang, Ning
中科院分区：
文献类型：
--
作者：
Chen, Yi;Wang, Mengyuan;Kang, Ning
间充质干细胞（MSCs）由于其自我更新能力以及分化为多种细胞谱系的潜力而具有巨大的治疗潜力。然而，如何提高间充质干细胞向成骨细胞的分化效率仍然是骨再生医学领域的一个重大挑战。在当前的研究中，我们确定了CHD7在间充质干细胞成骨分化中的作用。我们发现骨形态发生蛋白2（BMP2）或成骨诱导培养基可诱导间充质干细胞中CHD7的表达。通过小干扰RNA（siRNA）敲低间充质干细胞中的CHD7会导致关键成骨转录因子受到抑制，并损害间充质干细胞的成骨能力。相反，在间充质干细胞中过表达CHD7会使其成骨能力增强。从机制上讲，我们证明了CHD7与BMP信号通路的下游因子SMAD1相互作用。BMP2刺激CHD7与SP7增强子区域的结合。最后，在体内与支架共同培养时，CHD7沉默的间充质干细胞表现出成骨能力受损。总体而言，我们的研究建立了一种新的间充质干细胞成骨分化的表观遗传调控机制，并为控制间充质干细胞成骨提供了一个潜在靶点。（C）2016爱思唯尔公司。保留所有权利。
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.