Histone demethylase LSD1 regulates bone mass by controlling WNT7B and BMP2 signaling in osteoblasts | |
Sun, Jun1; Niu, Ningning1; Yan, Guang1; Yang, Yang1; Zou, Weiguo1; Ermann, Joerg2; Shi, Yujiang3,4 | |
刊名 | BONE RESEARCH |
2018 | |
卷号 | 6期号:14页码:- |
关键词 | Mesenchymal Stem-cells Brachydactyly Type A2 Gene-expression Differentiation Activation Mouse Methylation Repression Mutations Leukemia |
ISSN号 | 2095-4700 |
DOI | 10.1038/s41413-018-0015-x |
文献子类 | Article |
英文摘要 | Multiple regulatory mechanisms control osteoblast differentiation and function to ensure unperturbed skeletal formation and remodeling. In this study we identify histone lysine-specific demethylase 1(LSD1/KDM1A) as a key epigenetic regulator of osteoblast differentiation. Knockdown of LSD1 promoted osteoblast differentiation of human mesenchymal stem cells (hMSCs) in vitro and mice lacking LSD1 in mesenchymal cells displayed increased bone mass secondary to accelerated osteoblast differentiation. Mechanistic in vitro studies revealed that LSD1 epigenetically regulates the expression of WNT7B and BMP2. LSD1 deficiency resulted in increased BMP2 and WNT7B expression in osteoblasts and enhanced bone formation, while downregulation of WNT7B- and BMP2-related signaling using genetic mouse model or small-molecule inhibitors attenuated bone phenotype in vivo. Furthermore, the LSD1 inhibitor tranylcypromine (TCP) could increase bone mass in mice. These data identify LSD1 as a novel regulator of osteoblast activity and suggest LSD1 inhibition as a potential therapeutic target for treatment of osteoporosis. |
电子版国际标准刊号 | 2095-6231 |
WOS研究方向 | Cell & Tissue Engineering |
语种 | 英语 |
WOS记录号 | WOS:000431461000001 |
内容类型 | 期刊论文 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/3418] |
专题 | 生化所2018年发文 |
通讯作者 | Zou, Weiguo |
作者单位 | 1.Chinese Acad Sci, Univ Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol,State Key Lab C, 320 Yueyang Rd, Shanghai 200031, Peoples R China; 2.Harvard Med Sch, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA; 3.Harvard Med Sch, Boston Childrens Hosp, Newborn Med Div, Boston, MA 02115 USA; 4.Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA |
推荐引用方式 GB/T 7714 | Sun, Jun,Niu, Ningning,Yan, Guang,et al. Histone demethylase LSD1 regulates bone mass by controlling WNT7B and BMP2 signaling in osteoblasts[J]. BONE RESEARCH,2018,6(14):-. |
APA | Sun, Jun.,Niu, Ningning.,Yan, Guang.,Yang, Yang.,Zou, Weiguo.,...&Shi, Yujiang.(2018).Histone demethylase LSD1 regulates bone mass by controlling WNT7B and BMP2 signaling in osteoblasts.BONE RESEARCH,6(14),-. |
MLA | Sun, Jun,et al."Histone demethylase LSD1 regulates bone mass by controlling WNT7B and BMP2 signaling in osteoblasts".BONE RESEARCH 6.14(2018):-. |
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