PPARδ-mediated mitochondrial rewiring of osteoblasts determines bone mass.
Animals
Bone Density
/ physiology
Bone Remodeling
/ physiology
Cell Differentiation
Cells, Cultured
Energy Metabolism
/ genetics
Mesenchymal Stem Cells
/ cytology
Mice
Mice, Knockout
Mitochondria
/ metabolism
Osteoblasts
/ cytology
Osteoclasts
/ metabolism
Osteogenesis
/ physiology
Oxidative Phosphorylation
PPAR delta
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
21 05 2020
21 05 2020
Historique:
received:
03
12
2019
accepted:
27
04
2020
entrez:
23
5
2020
pubmed:
23
5
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Bone turnover, which is determined by osteoclast-mediated bone resorption and osteoblast-mediated bone formation, represents a highly energy consuming process. The metabolic requirements of osteoblast differentiation and mineralization, both essential for regular bone formation, however, remain incompletely understood. Here we identify the nuclear receptor peroxisome proliferator-activated receptor (PPAR) δ as key regulator of osteoblast metabolism. Induction of PPARδ was essential for the metabolic adaption and increased rate in mitochondrial respiration necessary for the differentiation and mineralization of osteoblasts. Osteoblast-specific deletion of PPARδ in mice, in turn, resulted in an altered energy homeostasis of osteoblasts, impaired mineralization and reduced bone mass. These data show that PPARδ acts as key regulator of osteoblast metabolism and highlight the relevance of cellular metabolic rewiring during osteoblast-mediated bone formation and bone-turnover.
Identifiants
pubmed: 32439961
doi: 10.1038/s41598-020-65305-5
pii: 10.1038/s41598-020-65305-5
pmc: PMC7242479
doi:
Substances chimiques
PPAR delta
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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