Programmed cell senescence in skeleton during late puberty

Nature Communications
Changjun LiMei Wan

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.

References

Sep 1, 1994·Developmental Biology·A M KachinskyJ B Miller
Oct 19, 2000·Baillière's Best Practice & Research. Clinical Endocrinology & Metabolism·C J Rosen
Mar 21, 2001·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·R P HeaneyC Weaver
May 16, 2003·Nature·Henry M Kronenberg
Jul 2, 2003·Molecular and Cellular Biology·Cecilia M SahlgrenJohn E Eriksson
Jan 7, 2004·Mechanisms of Development·Alexandra DelacourPedro Luis Herrera
Sep 24, 2004·Trends in Endocrinology and Metabolism : TEM·Ola Nilsson, Jeffrey Baron
Nov 19, 2005·Blood·Leonie M KammingaGerald de Haan
Apr 22, 2006·Aging Cell·Bo Yun LeeEun Seong Hwang
Aug 1, 1992·Trends in Endocrinology and Metabolism : TEM·C Cooper, L J Melton
Oct 28, 2008·The Journal of Surgical Research·Michael C CheungTeresa A Zimmers
Nov 6, 2009·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Filip CallewaertDirk Vanderschueren
Aug 13, 2010·Nature·Simón Méndez-FerrerPaul S Frenette
Oct 22, 2010·Stem Cells·Donghyun ParkBruce T Lahn
Aug 11, 2011·Cancer Research·Francesca AguiloMartin J Walsh
Dec 20, 2011·American Journal of Human Genetics·William T GibsonSteven J M Jones
Dec 23, 2011·Oncotarget·Katrina Tatton-BrownNazneen Rahman
Nov 19, 2013·Cell·Daniel Muñoz-EspínManuel Serrano
Mar 22, 2014·Nature·Saravana K RamasamyRalf H Adams
May 23, 2014·Nature·Jan M van Deursen
Aug 15, 2014·BoneKEy Reports·Sylvia ThieleMartina Rauner
Sep 23, 2014·Developmental Biology·Rebekah S DeckerMaurizio Pacifici
Nov 12, 2014·Nature Reviews. Rheumatology·René Rizzoli, Emmanuel Biver
Nov 25, 2014·Nature Cell Biology·Noriaki OnoHenry M Kronenberg
Dec 17, 2014·Developmental Cell·Marco DemariaJudith Campisi
Dec 24, 2014·Developmental Cell·Manuel Serrano
Jun 3, 2015·Nature Reviews. Endocrinology·Joshua N Farr, Sundeep Khosla

❮ Previous
Next ❯

Citations

Feb 13, 2018·Proceedings of the National Academy of Sciences of the United States of America·Yang ZhaoVera Gorbunova
Feb 10, 2018·The Journal of Clinical Endocrinology and Metabolism·Sundeep KhoslaJames L Kirkland
Jun 15, 2018·The Journal of Biological Chemistry·Amel DudakovicAndre J van Wijnen
Jul 13, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Guanqiao LiuXianrong Zhang
Apr 4, 2020·Annals of the New York Academy of Sciences·Yifan Zhao, Liang Xie
Sep 8, 2018·Nature Communications·Yanan ZhangAndy Peng Xiang
Sep 15, 2018·Scientific Reports·Takashi NoguchiLouis C Gerstenfeld
Dec 19, 2019·Frontiers in Immunology·Karan SachdevaPeisong Gao
Sep 17, 2020·Oxidative Medicine and Cellular Longevity·Yuang ZhangQixin Chen
Jul 25, 2018·Bone Research·Lei WangMei Wan
Feb 7, 2020·Cell & Bioscience·Jianhan RenChen Zhou
Jul 8, 2020·Cancers·Patrick M PerrigueMarek Figlerowicz
Oct 6, 2020·Frontiers in Cell and Developmental Biology·Hui PengMin Wang
Dec 24, 2019·Trends in Cell Biology·Bing-Dong SuiCheng-Hu Hu
Dec 15, 2020·Cell & Bioscience·Zhongwei LiJin Bai
Apr 8, 2021·Signal Transduction and Targeted Therapy·Tiantian WangChengqi He
Sep 12, 2021·Bone Research·Mei WanJennifer H Elisseeff
Sep 15, 2021·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·Z GongY Zhu
Aug 27, 2021·The Journal of Clinical Investigation·Lakshmi SanthanamMei Wan

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
fluorescence-activated cell sorting
PCR
immunoprecipitation
ChIP

Software Mentioned

NRecon
CTAn
CTVol
Primer3
SAS
CellQuest

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.