Oxylipin-PPARγ-initiated adipocyte senescence propagates secondary senescence in the bone marrow.
INK-family proteins
PPARγ
bone marrow adipocytes
bone marrow adiposity
cellular senescence
glucocorticoids
osteoporosis
oxylipins
prostaglandins
senescence-associated secretory phenotype
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
04 04 2023
04 04 2023
Historique:
received:
09
06
2022
revised:
12
01
2023
accepted:
06
03
2023
pmc-release:
04
04
2024
medline:
7
4
2023
entrez:
5
4
2023
pubmed:
6
4
2023
Statut:
ppublish
Résumé
The chronic use of glucocorticoids decreases bone mass and quality and increases bone-marrow adiposity, but the underlying mechanisms remain unclear. Here, we show that bone-marrow adipocyte (BMAd) lineage cells in adult mice undergo rapid cellular senescence upon glucocorticoid treatment. The senescent BMAds acquire a senescence-associated secretory phenotype, which spreads senescence in bone and bone marrow. Mechanistically, glucocorticoids increase the synthesis of oxylipins, such as 15d-PGJ2, for peroxisome proliferator-activated receptor gamma (PPARγ) activation. PPARγ stimulates the expression of key senescence genes and also promotes oxylipin synthesis in BMAds, forming a positive feedback loop. Transplanting senescent BMAds into the bone marrow of healthy mice is sufficient to induce the secondary spread of senescent cells and bone-loss phenotypes, whereas transplanting BMAds harboring a p16INK4a deletion did not show such effects. Thus, glucocorticoid treatment induces a lipid metabolic circuit that robustly triggers the senescence of BMAd lineage cells that, in turn, act as the mediators of glucocorticoid-induced bone deterioration.
Identifiants
pubmed: 37019080
pii: S1550-4131(23)00083-9
doi: 10.1016/j.cmet.2023.03.005
pmc: PMC10127143
mid: NIHMS1883407
pii:
doi:
Substances chimiques
PPAR gamma
0
Oxylipins
0
Glucocorticoids
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
667-684.e6Subventions
Organisme : NIA NIH HHS
ID : P01 AG066603
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG068226
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG072090
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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