Transcription factor HNF4 & alpha;2 promotes osteogenesis and prevents bone abnormalities in mice with renal osteodystrophy

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art_MARTINEZ-CALLE_Transcription_factor_HNF4_alpha2_promotes_osteogenesis_and_prevents_2023.PDF (12.86 MB)
Citações na Scopus
5
Tipo de produção
article
Data de publicação
2023
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
AMER SOC CLINICAL INVESTIGATION INC
Autores
MARTINEZ-CALLE, Marta
COURBON, Guillaume
HUNT-TOBEY, Bridget
FRANCIS, Connor
SPINDLER, Jadeah
WANG, Xueyan
SALUSKY, Isidro B.
MALLUCHE, Hartmut
Citação
JOURNAL OF CLINICAL INVESTIGATION, v.133, n.11, article ID e159928, 18p, 2023
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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 4 & alpha; (HNF4 & alpha;), a transcription factor mostly expressed in the liver, is also expressed in bone, and that osseous HNF4 & alpha; expression was dramatically reduced in patients and mice with ROD. Osteoblast-specific deletion of Hnf4 & alpha; resulted in impaired osteogenesis in cells and mice. Using multi-omics analyses of bones and cells lacking or overexpressing Hnf4 & alpha;1 and Hnf4 & alpha;2, we showed that HNF4 & alpha;2 is the main osseous Hnf4 & alpha; isoform that regulates osteogenesis, cell metabolism, and cell death. As a result, osteoblast-specific overexpression of Hnf4 & alpha;2 prevented bone loss in mice with CKD. Our results showed that HNF4 & alpha;2 is a transcriptional regulator of osteogenesis, implicated in the development of ROD.
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URI
https://observatorio.fm.usp.br/handle/OPI/54820
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Coleções
Artigos e Materiais de Revistas Científicas - FM/Outros
Artigos e Materiais de Revistas Científicas - LIM/16
Artigos e Materiais de Revistas Científicas - ODS/03