The orphan nuclear estrogen receptor-related receptor alpha (ERRalpha) is expressed throughout osteoblast differentiation and regulates bone formation in vitro.
The orphan nuclear estrogen receptor-related receptor alpha (ERRalpha) is expressed throughout osteoblast differentiation and regulates bone formation in vitro.
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孤儿雌激素受体相关受体α（Erralpha）在整个成骨细胞分化中表达，并在体外调节骨形成。
DOI：
10.1083/jcb.153.5.971
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发表时间：
2001-05-28
影响因子：
7.8
通讯作者：
Aubin, J E
中科院分区：
文献类型：
--
作者：
Bonnelye, E;Merdad, L;Kung, V;Aubin, J E
孤儿核雌激素受体相关受体α（ERRα）由许多细胞类型表达，但在成骨细胞中表达非常高，其中它反式激活至少一种成骨细胞相关基因骨桥蛋白。为了研究ERRα在骨中的假定参与，我们首先评估了其在体内大鼠颅骨（RC）和体外RC细胞中的表达。ERRα mRNA和蛋白在从早期骨祖细胞到成骨细胞的各个发育阶段均有表达，但蛋白在成熟的立方骨细胞中表达最丰富。为了评估ERRα在成骨细胞分化和骨形成中的功能作用，我们在增殖或分化的RC细胞培养物中通过反义寡核苷酸阻断其表达，并发现细胞生长抑制和增殖非依赖性分化抑制。另一方面，在RC细胞中ERRα过表达增加了祖细胞向成熟骨形成细胞的分化和成熟。我们的研究结果表明，ERRα在成骨细胞的发育过程中高度表达，并在增殖和分化阶段的分化和骨形成中发挥生理作用。此外，我们发现，在已知配体的情况下，受体水平的操纵是一个富有成效的方法，这种孤儿受体的功能分析和识别潜在的靶基因。
The orphan nuclear estrogen receptor–related receptor α (ERRα), is expressed by many cell types, but is very highly expressed by osteoblastic cells in which it transactivates at least one osteoblast-associated gene, osteopontin. To study the putative involvement of ERRα in bone, we first assessed its expression in rat calvaria (RC) in vivo and in RC cells in vitro. ERRα mRNA and protein were expressed at all developmental stages from early osteoprogenitors to bone-forming osteoblasts, but protein was most abundant in mature cuboidal osteoblasts. To assess a functional role for ERRα in osteoblast differentiation and bone formation, we blocked its expression by antisense oligonucleotides in either proliferating or differentiating RC cell cultures and found inhibition of cell growth and a proliferation-independent inhibition of differentiation. On the other hand, ERRα overexpression in RC cells increased differentiation and maturation of progenitors to mature bone-forming cells. Our findings show that ERRα is highly expressed throughout the osteoblast developmental sequence and plays a physiological role in differentiation and bone formation at both proliferation and differentiation stages. In addition, we found that manipulation of receptor levels in the absence of known ligand is a fruitful approach for functional analysis of this orphan receptor and identification of potential target genes.