Programmed cell senescence in skeleton during late puberty.
Nat Commun
; 8(1): 1312, 2017 11 03.
Article
in En
| MEDLINE
| ID: mdl-29101351
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sexual Maturation
/
Bone Development
/
Cellular Senescence
/
Enhancer of Zeste Homolog 2 Protein
Type of study:
Etiology_studies
Limits:
Adolescent
/
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2017
Document type:
Article
Affiliation country: