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学科主题口腔医学
The epigenetic promotion of osteogenic differentiation of human adipose-derived stem cells by the genetic and chemical blockade of histone demethylase LSD1
Ge, Wenshu1,2; Liu, Yunsong2; Chen, Tong2; Zhang, Xiao2; Lv, Longwei2; Jin, Chanyuan2; Jiang, Yong1; Shi, Lei3; Zhou, Yongsheng2,4
关键词Epigenetic Drug Human Adipose-derived Stem Cells Histone Methylation Osteogenic Differentiation Lysine-specific Demethylase 1
刊名BIOMATERIALS
2014-07-01
DOI10.1016/j.biomaterials.2014.04.055
35期:23页:6015-6025
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Engineering, Biomedical ; Materials Science, Biomaterials
研究领域[WOS]Engineering ; Materials Science
关键词[WOS]TRANSCRIPTION FACTOR OSTERIX ; STROMAL CELLS ; BREAST-CANCER ; IN-VIVO ; TISSUE ; METHYLATION ; REPRESSION ; INHIBITORS ; RUNX2 ; BONE
英文摘要

Human adipose-derived stem cells (hASCs) are a highly attractive source in bone tissue engineering. It has become increasingly clear that chromatin regulators play an important role in cell fate determination. However, how osteogenic differentiation of hASCs is controlled by epigenetic mechanisms is not fully understood. Here we use genetic tools and chemical inhibitors to modify the epigenetic program of hASCs and identify lysine-specific demethylase 1 (LSD1), a histone demethylase that specifically catalyzes demethylation of di- and mono- methyl histone H3 lysine 4 (H3K4me2/1), as a key regulator in osteogenic differentiation of hASCs. Specifically, we demonstrated that genetic depletion of LSD1 with lentiviral strategy for gene knockdown promoted osteogenic differentiation of hASCs by cell studies and xenograft assays. At the molecular level, we found that LSD1 regulates osteogenesis-associated genes expression through its histone demethylase activity. Significantly, we demonstrated LSD1 demethylase inhibitors could efficiently block its catalytic activity and epigenetically boost osteogenic differentiation of hASCs. Altogether, our study defined the functional and biological roles of LSD1 and extensively explored the effects of its enzymatic activity in osteogenic differentiation of hASCs. A better understanding of how LSD1 influences on osteogenesis associated epigenetic events will provide new insights into the modulation of hASCs based cell therapy and improve the development of bone tissue engineering with epigenetic intervention. (C) 2014 Elsevier Ltd. All rights reserved.

语种英语
WOS记录号WOS:000337212200004
项目编号81200763 ; 81070809 ; 81272284 ; 91219102 ; NCET-13-0934 ; NCET-11-0026
资助机构National Natural Science Foundation of China ; Program for New Century Excellent Talents (NCET) in University from Ministry of Education of China ; PKU School of Stomatolgy for talented young investigators ; National Health and Family Planning Commission of China
引用统计
被引频次:22[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/57954
专题北京大学口腔医学院_口腔修复科
北京大学口腔医学院_综合治疗二科
北京大学口腔医学院_第二门诊部
作者单位1.Peking Univ, Sch & Hosp Stomatol, Dept Gen Dent 2, Beijing 100081, Peoples R China
2.Peking Univ, Sch & Hosp Stomatol, Dept Prosthodont, Beijing 100081, Peoples R China
3.Tianjin Med Univ, Dept Biochem & Mol Biol, Tianjin Key Lab Med Epigenet, Tianjin 300070, Peoples R China
4.Peking Univ, Sch & Hosp Stomatol, Natl Engn Lab Digital & Mat Technol Stomatol, Beijing 100081, Peoples R China
推荐引用方式
GB/T 7714
Ge, Wenshu,Liu, Yunsong,Chen, Tong,et al. The epigenetic promotion of osteogenic differentiation of human adipose-derived stem cells by the genetic and chemical blockade of histone demethylase LSD1[J]. BIOMATERIALS,2014,35(23):6015-6025.
APA Ge, Wenshu.,Liu, Yunsong.,Chen, Tong.,Zhang, Xiao.,Lv, Longwei.,...&Zhou, Yongsheng.(2014).The epigenetic promotion of osteogenic differentiation of human adipose-derived stem cells by the genetic and chemical blockade of histone demethylase LSD1.BIOMATERIALS,35(23),6015-6025.
MLA Ge, Wenshu,et al."The epigenetic promotion of osteogenic differentiation of human adipose-derived stem cells by the genetic and chemical blockade of histone demethylase LSD1".BIOMATERIALS 35.23(2014):6015-6025.
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