Transcription factor HNF4α2 promotes osteogenesis and prevents bone abnormalities in mice with renal osteodystrophy.
Bone Biology
Bone disease
Chronic kidney disease
Metabolism
Journal
The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877
Informations de publication
Date de publication:
01 06 2023
01 06 2023
Historique:
received:
04
03
2022
accepted:
17
04
2023
medline:
2
6
2023
pubmed:
20
4
2023
entrez:
20
04
2023
Statut:
epublish
Résumé
Renal osteodystrophy (ROD) is a disorder of bone metabolism that affects virtually all patients with chronic kidney disease (CKD) and is associated with adverse clinical outcomes including fractures, cardiovascular events, and death. In this study, we showed that hepatocyte nuclear factor 4α (HNF4α), a transcription factor mostly expressed in the liver, is also expressed in bone, and that osseous HNF4α expression was dramatically reduced in patients and mice with ROD. Osteoblast-specific deletion of Hnf4α resulted in impaired osteogenesis in cells and mice. Using multi-omics analyses of bones and cells lacking or overexpressing Hnf4α1 and Hnf4α2, we showed that HNF4α2 is the main osseous Hnf4α isoform that regulates osteogenesis, cell metabolism, and cell death. As a result, osteoblast-specific overexpression of Hnf4α2 prevented bone loss in mice with CKD. Our results showed that HNF4α2 is a transcriptional regulator of osteogenesis, implicated in the development of ROD.
Identifiants
pubmed: 37079387
pii: 159928
doi: 10.1172/JCI159928
pmc: PMC10231994
doi:
pii:
Substances chimiques
Transcription Factors
0
Hepatocyte Nuclear Factor 4
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK101730
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK132657
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK132342
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK102815
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK114158
Pays : United States
Organisme : NIDDK NIH HHS
ID : R56 DK127986
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK131046
Pays : United States
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