Absence of Estrogen Receptor-Related-α Increases Osteoblastic Differentiation and Cancellous Bone Mineral Density
Absence of Estrogen Receptor-Related-α Increases Osteoblastic Differentiation and Cancellous Bone Mineral Density
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DOI：
10.1210/en.2009-0121
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发表时间：
2009-10-01
期刊：
影响因子：
4.8
通讯作者：
Fournier, B.
中科院分区：
文献类型：
--
作者：
Delhon, I.;Gutzwiller, S.;Fournier, B.
核孤儿受体人雌激素受体相关受体（ERR）-α与骨代谢有关。我们研究了ERR α沉默在人间充质干细胞（hMSCs）成骨细胞生成过程中的作用。我们发现，ERR α沉默导致骨唾液酸蛋白的增加和骨桥蛋白mRNA水平的降低，表明成骨细胞分化增强。这通过hMSC增加的存款钙的能力得到证实。同时，ERR α的敲低抑制脂肪形成，导致脂肪细胞数量和脂肪细胞标志物基因表达减少。与ERR α在骨代谢中的负面作用一致，我们发现成年雌性和雄性ERR α缺陷小鼠显示股骨松质骨体积和密度中度增加。这些动物的成骨细胞表面增加，骨髓脂肪体积减少。此外，ERR α缺陷的成骨细胞在体外表现出增加的分化特性，与我们在hMSC中的观察结果一致。总之，我们确定了ERR α通过影响成骨细胞分化在骨量调节中的作用。（内分泌学150：4463-4472，2009）
The nuclear orphan receptor human estrogen receptor-related receptor (ERR)-alpha is implicated in bone metabolism. We studied the effect of ERR alpha silencing in human mesenchymal stem cells (hMSCs) during osteoblastogenesis. We found that ERR alpha silencing led to an increase of bone sialoprotein and a decrease of osteopontin mRNA levels, suggesting enhanced osteoblastic differentiation. This was confirmed by an increased ability of hMSCs to deposit calcium. Concomitantly, knockdown of ERR alpha inhibited adipogenesis, resulting in a decrease in adipocyte number and adipocyte marker gene expression. In line with a negative role of ERR alpha in bone metabolism, we found that adult female and male ERR alpha-deficient mice displayed a moderate increase in femoral cancellous bone volume and density. Osteoblast surface was increased and marrow fat volume decreased in these animals. Furthermore, ERR alpha-deficient osteoblasts displayed increased differentiation properties in vitro in line with our observations in hMSCs. In summary, we identified a role for ERR alpha in bone mass regulation by affecting osteoblastic differentiation. (Endocrinology 150: 4463-4472, 2009)