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Retinoid X receptors orchestrate osteoclast differentiation and postnatal bone remodeling [SREBP]

ABSTRACT: Data from SREBP1c binding to the genome was visualized using Genome Browser (UCSC) in order to test its role in Mafb transcriptional regulation

ORGANISM(S): Mus musculus

PROVIDER: GSE63697 | GEO | 2015/02/04

SECONDARY ACCESSION(S): PRJNA268825

REPOSITORIES: GEO

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Retinoid X receptors orchestrate osteoclast differentiation and postnatal bone remodeling [SREBP]

Project description:Data from SREBP1c binding to the genome was visualized using Genome Browser (UCSC) in order to test its role in Mafb transcriptional regulation SREBP ChIP was performed in thioglycollate-elicited peritoneal macrophages treated as indicated.

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Retinoid X receptors orchestrate osteoclast differentiation and postnatal bone remodeling [RXR and PPARg]

Project description:Data from nuclear receptors RXR and PPARg binding to the genome was visualized using Genome Browser (UCSC) in order to test their role in Mafb transcriptional regulation

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Retinoid X receptors orchestrate osteoclast differentiation and postnatal bone remodeling.

Project description:Osteoclasts 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.

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Retinoid X receptors orchestrate osteoclast differentiation and postnatal bone remodeling

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-02-04 | E-GEOD-63698 | biostudies-arrayexpress

Retinoid X receptors orchestrate osteoclast differentiation and postnatal bone remodeling

Project description:This SuperSeries is composed of the SubSeries listed below.

2015-02-04 | GSE63698 | GEO

Microarrays analysis of SREBP-1a and SREBP-1c target genes identify new regulatory pathways.

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ChIP-Seq of Pax7 and Pax3 in myoblasts

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ChIP-Seq of Pax7 and Pax3 in myoblasts

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