2024-03-29T14:58:00Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/98892023-10-09T09:29:41Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2146
Repisalud
author
Menendez-Gutierrez, Maria Piedad
author
Roszer, Tamas
author
Fuentes, Lucia
author
Nunez, Vanessa
author
Escolano, Amelia
author
Redondo, Juan Miguel
author
De Clerck, Nora
author
Metzger, Daniel
author
Valledor, Annabel F
author
Ricote, Mercedes
funder
Ministerio de Economía y Competitividad (España)
funder
Unión Europea. Comisión Europea
funder
Fundación ProCNIC
2020-05-05T09:12:20Z
2020-05-05T09:12:20Z
2015-02
J Clin Invest. 2015; 125(2):809-23
0021-9738
http://hdl.handle.net/20.500.12105/9889
25574839
10.1172/JCI77186
1558-8238
The Journal of clinical investigation
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.
eng
Retinoid X receptors orchestrate osteoclast differentiation and postnatal bone remodeling
journal article
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URL
https://repisalud.isciii.es/bitstream/20.500.12105/9889/1/RetinoidXReceptorsOrchestrate_2015.pdf
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RetinoidXReceptorsOrchestrate_2015.pdf
URL
https://repisalud.isciii.es/bitstream/20.500.12105/9889/3/RetinoidXReceptorsOrchestrate_2015.pdf.txt
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RetinoidXReceptorsOrchestrate_2015.pdf.txt