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Nuclear receptor NR5A2 and bone: gene expression and association with bone mineral density

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Nuclear receptor NR5A2 and bone: gene expression and association with bone mineral density

dc.contributor.author	Riancho, José A	es_ES
dc.contributor.author	Liu, Yongjun	es_ES
dc.contributor.author	Sainz, Jesús	es_ES
dc.contributor.author	García-Pérez, Miguel A	es_ES
dc.contributor.author	Olmos, José M	es_ES
dc.contributor.author	Bolado-Carrancio, Alfonso	es_ES
dc.contributor.author	Valero, Carmen	es_ES
dc.contributor.author	Pérez-López, Javier	es_ES
dc.contributor.author	Cano, Antonio	es_ES
dc.contributor.author	Yang, Tielin	es_ES
dc.contributor.author	Sañudo, Carolina	es_ES
dc.contributor.author	Deng, Hong-Wen	es_ES
dc.contributor.author	Rodríguez-Rey, José C	es_ES
dc.date.accessioned	2015-06-19T10:17:56Z
dc.date.available	2015-06-19T10:17:56Z
dc.date.issued	2012	es_ES
dc.identifier.citation	European journal of endocrinology / European Federation of Endocrine Societies Vol. 166 Issue 1: pp. 69-75	es_ES
dc.identifier.uri	http://hdl.handle.net/10550/44525
dc.description.abstract	ObjectiveThere is growing evidence for a link between energy and bone metabolism. The nuclear receptor subfamily 5 member A2 (NR5A2) is involved in lipid metabolism and modulates the expression of estrogen-related genes in some tissues. The objective of this study was to explore the influence of NR5A2 on bone cells and to determine whether its allelic variations are associated with bone mineral density (BMD).DesignAnalyses of gene expression by quantitative PCR and inhibition of NR5A2 expression by siRNAs were used to explore the effects of NR5A2 in osteoblasts. Femoral neck BMD and 30 single nucleotide polymorphisms (SNPs) were first analyzed in 935 postmenopausal women and the association of NR5A2 genetic variants with BMD was explored in other 1284 women in replication cohorts.ResultsNR5A2 was highly expressed in bone. The inhibition of NR5A2 confirmed that it modulates the expression of osteocalcin, osteoprotegerin, and podoplanin in osteoblasts. Two SNPs were associated with BMD in the Spanish discovery cohort (rs6663479, P=0.0014, and rs2816948, P=0.0012). A similar trend was observed in another Spanish cohort, with statistically significant differences across genotypes in the combined analysis (P=0.03). However, the association in a cohort from the United States was rather weak. Electrophoretic mobility assays and studies with luciferase reporter vectors confirmed the existence of differences in the binding of nuclear proteins and the transcriptional activity of rs2816948 alleles.ConclusionsNR5A2 modulates gene expression in osteoblasts and some allelic variants are associated with bone mass in Spanish postmenopausal women.	es_ES
dc.title	Nuclear receptor NR5A2 and bone: gene expression and association with bone mineral density	es_ES
dc.type	journal article	es_ES
dc.identifier.doi	10.1530/EJE-11-0571	es_ES
dc.identifier.idgrec	068532	es_ES