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Cited by 92Telomeres, Telomerase, and SenescenceMesenchymal stem cell researchBone Metabolism and Diseases

Programmed cell senescence in skeleton during late puberty

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Li, Changjun, Chai, Yu, Wang, Lei, Gao, Bo, Chen, Hao, Gao, Peisong, Zhou, Feng-Quan, Luo, Xianghang +4 more·2017·Nature Communications
DOI 10.1038/s41467-017-01509-0PMC PMC5670205
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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.

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  • In late puberty, mesenchymal stem/progenitor cells undergo normal programmed senescence indicated by loss of nestin expression.

    “In late puberty, mesenchymal stem/progenitor cells undergo normal programmed senescence, indicated by the loss of nestin expression199.”

    From SenNet recommendations for detecting senescent cells in different tissues (2024) · cites this paper as [199]

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Cited by

Sorted by citations

Authors
Li, C., Chai, Y., Wang, L., Gao, B., Chen, H., Gao, P., Zhou, F.-Q., Luo, X., Crane, J. L., Yu, B., Cao, X., & Wan, M.
Affiliations
  • Central South University (CN)
  • Johns Hopkins University (US)
  • Nanfang Hospital (CN)
Corresponding author
  • Yu, Bin
  • Wan, Mei
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2017-11-03
Volume
8
Issue
1
Pages
1312-1312
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-017-01509-0
PMC
PMC5670205
OpenAlex
W2766920800
Cited by
92
References
8
Citations by year
2026: 5 · 2025: 8 · 2024: 12 · 2023: 10 · 2022: 10 · 2021: 11 · 2020: 17 · 2019: 9 · 2018: 10
FWCI
7.29
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Johns Hopkins University
  • National Institutes of Health
  • National Eye Institute (R01EY027347)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK083350)
  • National Institute of Neurological Disorders and Stroke (R01NS085176)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (K08AR064833)
  • Department of Surgery, School of Medicine, Johns Hopkins University
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Keywords
mesenchymal stem/progenitor cells, delayed puberty, EZH2, H3K27me3, nestin, bone formation, osteoporosis
MeSH terms
Enhancer of Zeste Homolog 2 Protein, Adolescent, Animals, Bone Development, Female, Histones, Humans, Male, Methylation, Mice, Transgenic, Osteogenesis, Osteoporosis, Puberty, Sexual Maturation, Cellular Senescence, Mice, Knockout, Epigenesis, Genetic, Mice, Mesenchymal Stem Cells, Nestin

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