Department of Internal Medicine, Hospital U.M. Valdecilla-IFIMAV, University of Cantabria, RETICEF, Avenida de Valdecilla S/N, 39008 Santander, Spain.
Eur J Endocrinol. 2012 Jan;166(1):69-75. doi: 10.1530/EJE-11-0571. Epub 2011 Nov 2.
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).
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.
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.
NR5A2 modulates gene expression in osteoblasts and some allelic variants are associated with bone mass in Spanish postmenopausal women.
越来越多的证据表明能量与骨代谢之间存在关联。核受体亚家族 5 成员 A2（NR5A2）参与脂质代谢，并调节某些组织中雌激素相关基因的表达。本研究旨在探讨 NR5A2 对骨细胞的影响，并确定其等位基因变异是否与骨密度（BMD）相关。
通过定量 PCR 分析基因表达和 siRNA 抑制 NR5A2 表达来探索 NR5A2 在成骨细胞中的作用。首先在 935 名绝经后妇女中分析股骨颈 BMD 和 30 个单核苷酸多态性（SNP），并在其他 1284 名复制队列中的妇女中探索 NR5A2 遗传变异与 BMD 的关联。
NR5A2 在骨中高表达。抑制 NR5A2 证实它调节成骨细胞中骨钙素、骨保护素和 podoplanin 的表达。两个 SNP 与西班牙发现队列中的 BMD 相关（rs6663479，P=0.0014，和 rs2816948，P=0.0012）。在另一个西班牙队列中观察到类似的趋势，在联合分析中基因型之间存在统计学显著差异（P=0.03）。然而，在美国队列中的关联较弱。电泳迁移率分析和荧光素酶报告载体研究证实 rs2816948 等位基因的核蛋白结合和转录活性存在差异。
NR5A2 调节成骨细胞中的基因表达，一些等位基因变异与西班牙绝经后妇女的骨量相关。
