Programmed cell senescence in skeleton during late puberty

Changjun Li, Yu Chai, Lei Wang, Bo Gao, Hao Chen, Peisong Gao, Feng Quan Zhou, Xianghang Luo, Janet L. Crane, Bin Yu, Xu Cao, Mei Wan

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number1312
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General
  • General Physics and Astronomy

Fingerprint

Dive into the research topics of 'Programmed cell senescence in skeleton during late puberty'. Together they form a unique fingerprint.

Cite this