Transcription factor HNF4α2 promotes osteogenesis and prevents bone abnormalities in mice with renal osteodystrophy

Marta Martinez-Calle, Guillaume Courbon, Bridget Hunt-Tobey, Connor Francis, Jadeah Spindler, Xueyan Wang, Luciene M. dos Reis, Carolina S.W. Martins, Isidro B. Salusky, Hartmut Malluche, Thomas L. Nickolas, Rosa M.A. Moyses, Aline Martin, Valentin David

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere159928
JournalJournal of Clinical Investigation
Volume133
Issue number11
DOIs
StatePublished - Jun 1 2023

Bibliographical note

Publisher Copyright:
Copyright: © 2023, Martinez-Calle et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.

ASJC Scopus subject areas

  • General Medicine

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