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5-Azacytidine facilitates osteogenic gene expression and differentiation of mesenchymal stem cells by alteration in DNA methylation

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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.

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Acknowledgments

This work was supported by grant J20020579-30116 from the Key Science and Technology Foundation of Zhejiang Province, People’s Republic of China.

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Authors and Affiliations

  1. Key Laboratory of Molecular Medicine, Huzhou Central Hospital, 313100, Huzhou, Zhejiang, People’s Republic of China

    Guo-Shun Zhou & Li-Cheng Dai

  2. College of Life Sciences, Zhejiang University, 310058, Hangzhou, People’s Republic of China

    Xiao-Lei Zhang, Jun-Ping Wu, Rui-Peng Zhang, Li-Xin Xiang & Jian-Zhong Shao

  3. Key Lab for Cell and Gene Engineering of Zhejiang Province, Hangzhou, People’s Republic of China

    Xiao-Lei Zhang, Jun-Ping Wu, Rui-Peng Zhang, Li-Xin Xiang & Jian-Zhong Shao

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  1. Guo-Shun Zhou
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Correspondence to Guo-Shun Zhou or Jian-Zhong Shao.

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Guo-Shun Zhou and Xiao-Lei Zhang contributed equally.

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Zhou, GS., Zhang, XL., Wu, JP. et al. 5-Azacytidine facilitates osteogenic gene expression and differentiation of mesenchymal stem cells by alteration in DNA methylation. Cytotechnology 60, 11–22 (2009). https://doi.org/10.1007/s10616-009-9203-2

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  • DOI: https://doi.org/10.1007/s10616-009-9203-2

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