title: 5-Azacytidine facilitates osteogenic gene expression and differentiation of mesenchymal stem cells by alteration in DNA methylation.
abstract: Mesenchymal stem cells (MSCs) are considered to be one of the most promising therapeutic cell sources as they encompass a plasticity of multiple cell lineages. The challenge in using these cells lies in developing well-defined protocols for directing cellular differentiation to generate a desired lineage. In this study, we investigated the effect of 5-azacytidine, a DNA demethylating agent, on osteogenic differentiation of MSCs. The cells were exposed to 5-azacytidine in culture medium for 24 h prior to osteogenic induction. Osteogenic differentiation was determined by several the appearance of a number of osteogenesis characteristics, including gene expression, ALP activity, and calcium mineralization. Pretreatment of MSCs with 5-azacytidine significantly facilitated osteogenic differentiation and was accompanied by hypomethylation of genomic DNA and increased osteogenic gene expression. Taking dlx5 as a representative, methylation alterations of the "CpG island shore" in the promoter caused by 5-azacytidine appeared to contribute to osteogenic differentiation.
authors: Key Laboratory of Molecular Medicine, Huzhou Central Hospital, 313100, Huzhou, Zhejiang, People's Republic of China. gfz@mail.huptt.zj.cn.
authors: Guo-Shun
authors: GS
authors: Zhou
authors: College of Life Sciences, Zhejiang University, 310058, Hangzhou, People's Republic of China.|Key Lab for Cell and Gene Engineering of Zhejiang Province, Hangzhou, People's Republic of China.
authors: Xiao-Lei
authors: XL
authors: Zhang
authors: College of Life Sciences, Zhejiang University, 310058, Hangzhou, People's Republic of China.|Key Lab for Cell and Gene Engineering of Zhejiang Province, Hangzhou, People's Republic of China.
authors: Jun-Ping
authors: JP
authors: Wu
authors: College of Life Sciences, Zhejiang University, 310058, Hangzhou, People's Republic of China.|Key Lab for Cell and Gene Engineering of Zhejiang Province, Hangzhou, People's Republic of China.
authors: Rui-Peng
authors: RP
authors: Zhang
authors: College of Life Sciences, Zhejiang University, 310058, Hangzhou, People's Republic of China.|Key Lab for Cell and Gene Engineering of Zhejiang Province, Hangzhou, People's Republic of China.
authors: Li-Xin
authors: LX
authors: Xiang
authors: Key Laboratory of Molecular Medicine, Huzhou Central Hospital, 313100, Huzhou, Zhejiang, People's Republic of China.
authors: Li-Cheng
authors: LC
authors: Dai
authors: College of Life Sciences, Zhejiang University, 310058, Hangzhou, People's Republic of China. shaojz@zju.edu.cn.|Key Lab for Cell and Gene Engineering of Zhejiang Province, Hangzhou, People's Republic of China. shaojz@zju.edu.cn.
authors: Jian-Zhong
authors: JZ
authors: Shao