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

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorMARTINEZ-CALLE, Marta
dc.contributor.authorCOURBON, Guillaume
dc.contributor.authorHUNT-TOBEY, Bridget
dc.contributor.authorFRANCIS, Connor
dc.contributor.authorSPINDLER, Jadeah
dc.contributor.authorWANG, Xueyan
dc.contributor.authorREIS, Luciene M. dos
dc.contributor.authorMARTINS, Carolina S. W.
dc.contributor.authorSALUSKY, Isidro B.
dc.contributor.authorMALLUCHE, Hartmut
dc.contributor.authorNICKOLAS, Thomas L.
dc.contributor.authorMOYSES, Rosa M. A.
dc.contributor.authorDAVID, Valentin
dc.contributor.authorMARTIN, Aline
dc.date.accessioned2023-08-16T18:03:15Z
dc.date.available2023-08-16T18:03:15Z
dc.date.issued2023
dc.description.abstractRenal 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.eng
dc.description.indexMEDLINE
dc.description.indexPubMed
dc.description.indexWoS
dc.description.indexScopus
dc.description.sponsorshipNational Institutes of Health [R01DK102815, R01DK114158, R01DK132657, R01DK101730, R01DK131046, R56DK127986]
dc.description.sponsorshipNIH/NIDDK [P30DK114857]
dc.identifier.citationJOURNAL OF CLINICAL INVESTIGATION, v.133, n.11, article ID e159928, 18p, 2023
dc.identifier.doi10.1172/JCI159928
dc.identifier.eissn1558-8238
dc.identifier.issn0021-9738
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/54820
dc.language.isoeng
dc.publisherAMER SOC CLINICAL INVESTIGATION INCeng
dc.relation.ispartofJournal of Clinical Investigation
dc.rightsopenAccesseng
dc.rights.holderCopyright AMER SOC CLINICAL INVESTIGATION INCeng
dc.subject.othernuclear factor 4-alphaeng
dc.subject.othergenome-wide associationeng
dc.subject.otherchronic kidney-diseaseeng
dc.subject.othergene-expressioneng
dc.subject.othermouse modeleng
dc.subject.otherhip fractureeng
dc.subject.otherp1 promotereng
dc.subject.otherlivereng
dc.subject.otherisoformseng
dc.subject.othermetabolismeng
dc.subject.wosMedicine, Research & Experimentaleng
dc.titleTranscription factor HNF4 & alpha;2 promotes osteogenesis and prevents bone abnormalities in mice with renal osteodystrophyeng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisous
hcfmusp.author.externalMARTINEZ-CALLE, Marta:Northwestern Univ, Inst Publ Hlth & Med,Feinberg Sch Med, Ctr Translat Metab & Hlth, Dept Med, Chicago, IL USA
hcfmusp.author.externalCOURBON, Guillaume:Northwestern Univ, Inst Publ Hlth & Med,Feinberg Sch Med, Ctr Translat Metab & Hlth, Dept Med, Chicago, IL USA
hcfmusp.author.externalHUNT-TOBEY, Bridget:Northwestern Univ, Inst Publ Hlth & Med,Feinberg Sch Med, Ctr Translat Metab & Hlth, Dept Med, Chicago, IL USA
hcfmusp.author.externalFRANCIS, Connor:Northwestern Univ, Inst Publ Hlth & Med,Feinberg Sch Med, Ctr Translat Metab & Hlth, Dept Med, Chicago, IL USA
hcfmusp.author.externalSPINDLER, Jadeah:Northwestern Univ, Inst Publ Hlth & Med,Feinberg Sch Med, Ctr Translat Metab & Hlth, Dept Med, Chicago, IL USA
hcfmusp.author.externalWANG, Xueyan:Northwestern Univ, Inst Publ Hlth & Med,Feinberg Sch Med, Ctr Translat Metab & Hlth, Dept Med, Chicago, IL USA
hcfmusp.author.externalSALUSKY, Isidro B.:UCLA, David Geffen Sch Med, Dept Pediat, Los Angeles, CA USA
hcfmusp.author.externalMALLUCHE, Hartmut:Univ Kentucky, Dept Internal Med, Div Nephrol Bone & Mineral Metab, Lexington, KY USA
hcfmusp.author.externalDAVID, Valentin:Northwestern Univ, Inst Publ Hlth & Med,Feinberg Sch Med, Ctr Translat Metab & Hlth, Dept Med, Chicago, IL USA; Northwestern Univ, Ctr Translat Metab & Hlth, Div Nephrol & Hypertens, Feinberg Sch Med, 320 East Super St,Searle Bldg,Suite 10-517, Chicago, IL 60611 USA
hcfmusp.citation.scopus6
hcfmusp.contributor.author-fmusphcLUCIENE MACHADO DOS REIS
hcfmusp.contributor.author-fmusphcCAROLINA STELLER WAGNER MARTINS
hcfmusp.contributor.author-fmusphcROSA MARIA AFFONSO MOYSES
hcfmusp.description.articlenumbere159928
hcfmusp.description.issue11
hcfmusp.description.volume133
hcfmusp.origemWOS
hcfmusp.origem.pubmed37079387
hcfmusp.origem.scopus2-s2.0-85160966549
hcfmusp.origem.wosWOS:001021715500024
hcfmusp.publisher.cityANN ARBOReng
hcfmusp.publisher.countryUSAeng
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