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dc.contributor.authorMenéndez-Gutiérrez, María Piedad 
dc.contributor.authorRoszer, Tamas 
dc.contributor.authorFuentes, Lucia 
dc.contributor.authorNunez, Vanessa 
dc.contributor.authorEscolano, Amelia 
dc.contributor.authorRedondo, Juan Miguel 
dc.contributor.authorDe Clerck, Nora
dc.contributor.authorMetzger, Daniel
dc.contributor.authorValledor, Annabel F
dc.contributor.authorRicote, Mercedes
dc.identifier.citationJ Clin Invest. 2015; 125(2):809-23es_ES
dc.description.abstractOsteoclasts are bone-resorbing cells that are important for maintenance of bone remodeling and mineral homeostasis. Regulation of osteoclast differentiation and activity is important for the pathogenesis and treatment of diseases associated with bone loss. Here, we demonstrate that retinoid X receptors (RXRs) are key elements of the transcriptional program of differentiating osteoclasts. Loss of RXR function in hematopoietic cells resulted in formation of giant, nonresorbing osteoclasts and increased bone mass in male mice and protected female mice from bone loss following ovariectomy, which induces osteoporosis in WT females. The increase in bone mass associated with RXR deficiency was due to lack of expression of the RXR-dependent transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B (MAFB) in osteoclast progenitors. Evaluation of osteoclast progenitor cells revealed that RXR homodimers directly target and bind to the Mafb promoter, and this interaction is required for proper osteoclast proliferation, differentiation, and activity. Pharmacological activation of RXRs inhibited osteoclast differentiation due to the formation of RXR/liver X receptor (LXR) heterodimers, which induced expression of sterol regulatory element binding protein-1c (SREBP-1c), resulting in indirect MAFB upregulation. Our study reveals that RXR signaling mediates bone homeostasis and suggests that RXRs have potential as targets for the treatment of bone pathologies such as osteoporosis.es_ES
dc.description.sponsorshipThis work was supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2012-31483 to M. Ricote; SAF2011-23402 to A.F. Valledor), a Juan de la Cierva Program and an FP7 Marie Curie Career Integration Grant (to L. Fuentes), and an FP7 Marie Curie IEF Grant and a European Study for Diabetes-Lilly Research Program grant (to T. Rőszer). The CNIC is supported by the Spanish Ministry of Economy and Competitiveness and the Pro-CNIC Foundationes_ES
dc.publisherAmerican Society for Clinical Investigationes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subject.meshAnimals es_ES
dc.subject.meshBone Remodeling es_ES
dc.subject.meshCell Differentiation es_ES
dc.subject.meshFemale es_ES
dc.subject.meshLiver X Receptors es_ES
dc.subject.meshMafB Transcription Factor es_ES
dc.subject.meshMale es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Knockout es_ES
dc.subject.meshOrphan Nuclear Receptors es_ES
dc.subject.meshOsteoclasts es_ES
dc.subject.meshOsteoporosis es_ES
dc.subject.meshProtein Multimerization es_ES
dc.subject.meshRetinoid X Receptors es_ES
dc.subject.meshStem Cells es_ES
dc.subject.meshSterol Regulatory Element Binding Protein 1 es_ES
dc.subject.meshTranscription, Genetices_ES
dc.subject.meshUp-Regulation es_ES
dc.titleRetinoid X receptors orchestrate osteoclast differentiation and postnatal bone remodelinges_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderEuropean Commisiones_ES
dc.contributor.funderFundación ProCNICes_ES
dc.identifier.journalThe Journal of clinical investigationes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Regulación Génica en Remodelado Vascular e Inflamaciónes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Señalización de los Receptores Nucleareses_ES

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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
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