EBF2 regulates osteoblast-dependent differentiation of osteoclasts
EBF2 regulates osteoblast-dependent differentiation of osteoclasts
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DOI：
10.1016/j.devcel.2005.10.009
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发表时间：
2005-12-01
影响因子：
11.8
通讯作者：
Grosschedl, R
中科院分区：
文献类型：
--
作者：
Kieslinger, M;Folberth, S;Grosschedl, R
骨沉积成骨细胞和骨吸收破骨细胞之间的沟通是骨发育和体内平衡所必需的。在这里，我们确定EBF 2，早期B细胞因子（EBF）家族的转录因子，在成骨细胞祖细胞中表达的成员，作为破骨细胞分化的调节器。我们发现Ebf 2靶向失活纯合子小鼠显示骨量减少和破骨细胞数量增加。这些缺陷伴随着编码RANK诱饵受体的骨保护素（Opg）基因的显著下调。EBF 2结合Opg启动子中的序列，并与Wnt响应性LEF 1/TCF：β-连环蛋白途径协同反式激活Opg启动子。总之，这些数据确定EBF 2作为RANK-RANKL信号传导和破骨细胞的成骨细胞依赖性分化的调节剂。
Communication between bone-depositing osteoblasts and bone-resorbing osteoclasts is required for bone development and homeostasis. Here, we identify EBF2, a member of the early B cell factor (EBF) family of transcription factors that is expressed in osteoblast progenitors, as a regulator of osteoclast differentiation. We find that mice homozygous for a targeted inactivation of Ebf2 show reduced bone mass and an increase in the number of osteoclasts. These defects are accompanied by a marked downregulation of the osteoprotegerin (Opg) gene, encoding a RANK decoy receptor. EBF2 binds to sequences in the Opg promoter and transactivates the Opg promoter in synergy with the Wnt-responsive LEF1/TCF:beta-catenin pathway. Taken together, these data identify EBF2 as a regulator of RANK-RANKL signaling and osteoblast-dependent-differentiation of osteoclasts.