Programmed cell senescence in skeleton during late puberty

被引：85

作者：

Li, Changjun ^{[1
,2
]}

Chai, Yu ^{[1
,3
]}

Wang, Lei ^{[1
,3
]}

Gao, Bo ^{[1
]}

Chen, Hao ^{[1
]}

Gao, Peisong ^{[4
]}

Zhou, Feng-Quan ^{[1
]}

Luo, Xianghang

Crane, Janet L. ^{[1
,5
]}

Yu, Bin ^{[3
]}

Cao, Xu ^{[1
]}

Wan, Mei ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Orthopaed Surg, Baltimore, MD 21205 USA

[2] Cent S Univ, Xiangya Hosp, Endocrinol Res Ctr, Dept Endocrinol, Changsha 410008, Hunan, Peoples R China

[3] Southern Med Univ, Nanfang Hosp, Dept Orthopaed & Traumatol, Guangzhou 510515, Guangdong, Peoples R China

[4] Johns Hopkins Univ, Sch Med, Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD 21224 USA

[5] Johns Hopkins Univ, Sch Med, Dept Pediat Endocrinol, Baltimore, MD 21205 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

美国国家卫生研究院;

关键词：

MESENCHYMAL STEM-CELLS; LONGITUDINAL BONE-GROWTH; CAUSE WEAVER SYNDROME; OSTEOGENIC DIFFERENTIATION; STROMAL CELLS; SELF-RENEWAL; LIFE-SPAN; EZH2; MARROW; NESTIN;

D O I：

10.1038/s41467-017-01509-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Mesenchymal stem/progenitor cells (MSPCs) undergo rapid self-renewal and differentiation, contributing to fast skeletal growth during childhood and puberty. It remains unclear whether these cells change their properties during late puberty to young adulthood, when bone growth and accrual decelerate. Here we show that MSPCs in primary spongiosa of long bone in mice at late puberty undergo normal programmed senescence, characterized by loss of nestin expression. MSPC senescence is epigenetically controlled by the polycomb histone methyltransferase enhancer of zeste homolog 2 (Ezh2) and its trimethylation of histone H3 on Lysine 27 (H3K27me3) mark. Ezh2 maintains the repression of key cell senescence inducer genes through H3K27me3, and deletion of Ezh2 in early pubertal mice results in premature cellular senescence, depleted MSPCs pool, and impaired osteogenesis as well as osteoporosis in later life. Our data reveals a programmed cell fate change in postnatal skeleton and unravels a regulatory mechanism underlying this phenomenon.

引用

页数：15

共 67 条

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