Vitamin C epigenetically controls osteogenesis and bone mineralization.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
06 10 2022
06 10 2022
Historique:
received:
01
10
2020
accepted:
09
08
2022
entrez:
6
10
2022
pubmed:
7
10
2022
medline:
12
10
2022
Statut:
epublish
Résumé
Vitamin C deficiency disrupts the integrity of connective tissues including bone. For decades this function has been primarily attributed to Vitamin C as a cofactor for collagen maturation. Here, we demonstrate that Vitamin C epigenetically orchestrates osteogenic differentiation and function by modulating chromatin accessibility and priming transcriptional activity. Vitamin C regulates histone demethylation (H3K9me3 and H3K27me3) and promotes TET-mediated 5hmC DNA hydroxymethylation at promoters, enhancers and super-enhancers near bone-specific genes. This epigenetic circuit licenses osteoblastogenesis by permitting the expression of all major pro-osteogenic genes. Osteogenic cell differentiation is strictly and continuously dependent on Vitamin C, whereas Vitamin C is dispensable for adipogenesis. Importantly, deletion of 5hmC-writers, Tet1 and Tet2, in Vitamin C-sufficient murine bone causes severe skeletal defects which mimic bone phenotypes of Vitamin C-insufficient Gulo knockout mice, a model of Vitamin C deficiency and scurvy. Thus, Vitamin C's epigenetic functions are central to osteoblastogenesis and bone formation and may be leveraged to prevent common bone-degenerating conditions.
Identifiants
pubmed: 36202795
doi: 10.1038/s41467-022-32915-8
pii: 10.1038/s41467-022-32915-8
pmc: PMC9537512
doi:
Substances chimiques
Chromatin
0
Histones
0
DNA
9007-49-2
Ascorbic Acid
PQ6CK8PD0R
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
5883Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK131455
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK126827
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK058185
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR049069
Pays : United States
Informations de copyright
© 2022. The Author(s).
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