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学科主题: 口腔医学
题名:
The epigenetic promotion of osteogenic differentiation of human adipose-derived stem cells by the genetic and chemical blockade of histone demethylase LSD1
作者: 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
发表日期: 2014-07-01
DOI: 10.1016/j.biomaterials.2014.04.055
卷: 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
所属项目编号: 81200763 ; 81070809 ; 81272284 ; 91219102 ; NCET-13-0934 ; NCET-11-0026
项目资助者: 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
WOS记录号: WOS:000337212200004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57954
Appears in Collections:北京大学口腔医学院_口腔修复科_期刊论文

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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

Recommended Citation:
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.
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