title: Nuclear receptor NR5A2 and bone: gene expression and association with bone mineral density.
abstract: OBJECTIVE
  There 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).
  
  
  METHODS
  Analyses 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.
  
  
  RESULTS
  NR5A2 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.
  
  
  CONCLUSIONS
  NR5A2 modulates gene expression in osteoblasts and some allelic variants are associated with bone mass in Spanish postmenopausal women.
authors: Department of Internal Medicine, Hospital U.M. Valdecilla-IFIMAV, University of Cantabria, RETICEF, Avenida de Valdecilla S/N, 39008 Santander, Spain. rianchoj@unican.es
authors: José A
authors: JA
authors: Riancho
authors: Yongjun
authors: Y
authors: Liu
authors: Jesús
authors: J
authors: Sainz
authors: Miguel A
authors: MA
authors: García-Pérez
authors: José M
authors: JM
authors: Olmos
authors: Alfonso
authors: A
authors: Bolado-Carrancio
authors: Carmen
authors: C
authors: Valero
authors: Javier
authors: J
authors: Pérez-López
authors: Antonio
authors: A
authors: Cano
authors: Tielin
authors: T
authors: Yang
authors: Carolina
authors: C
authors: Sañudo
authors: Hong-Wen
authors: HW
authors: Deng
authors: José C
authors: JC
authors: Rodríguez-Rey
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000235:genetics*; D001842:Bone and Bones / Q000378:metabolism*; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D010006:Osteoblasts / Q000378:metabolism; D017698:Postmenopause; D011401:Promoter Regions, Genetic / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*
chemical_list: C082631:NR5A2 protein, human; D018160:Receptors, Cytoplasmic and Nuclear