Wdr5, a WD-40 protein, regulates osteoblast differentiation during embryonic bone development
Wdr5, a WD-40 protein, regulates osteoblast differentiation during embryonic bone development
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DOI：
10.1016/j.ydbio.2006.02.031
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发表时间：
2006-07-15
影响因子：
2.7
通讯作者：
Demay, Marie B.
中科院分区：
文献类型：
--
作者：
Gori, Francesca;Friedman, Lauren G.;Demay, Marie B.
Wdr 5在体外加速成骨细胞和软骨细胞的分化，并且在成骨细胞以及增殖和肥大的软骨细胞中发育性表达。为了研究Wdr 5在软骨内骨发育过程中的作用，产生了在小鼠α（1）I胶原启动子的2.3-kb片段控制下过表达Wdr 5的转基因小鼠。该转基因在转基因阳性小鼠的成骨细胞中特异性表达，但在生长板中不存在。在胚胎第14.5天的组织学分析表明，转基因阳性胚胎的肱骨长于从野生型同窝仔中分离的肱骨，这主要是由于肥大软骨细胞层的扩张。观察到成骨细胞分化的加速，在转基因阳性胚胎的骨领中I型胶原的表达更大、更广泛，矿物质沉积更广泛。在转基因阳性小鼠中也观察到血管侵袭的加速。转基因小鼠的出生后分析证实了成骨细胞分化的持续加速。靶向表达Wdr 5的成骨细胞导致早期激活的典型。骨领和原代颅骨成骨细胞培养中的Wnt信号通路。此外，Wdr 5的过表达增加了OPG的表达，OPG是经典Wnt信号通路的靶点。总的来说，我们的研究结果表明，Wdr 5加速成骨细胞分化与经典Wnt通路的激活。(c)2006年爱思唯尔公司All rights reserved.
Wdr5 accelerates osteoblast and chondrocyte differentiation in vitro, and is developmentally expressed in osteoblasts as well as in proliferating and hypertrophic chondrocytes. To investigate the role of Wdr5 during endochondral bone development, transgenic mice overexpressing Wdr5 under the control of the 2.3-kb fragment of the mouse alpha(1) I collagen promoter were generated. The transgene was specifically expressed in the osteoblasts of transgene positive mice and was absent in the growth plate. Histological analyses at embryonic day 14.5 demonstrated that the humeri of transgene positive embryos were longer than those isolated from wild-type littermates largely due to an expansion of the hypertrophic chondrocyte layer. Acceleration of osteoblast differentiation was observed with greater and more extensive expression of type I collagen and more extensive mineral deposition in the bone collar of transgene positive embryos. Acceleration of vascular invasion was also observed in transgene positive mice. Postnatal analyses of transgenic mice confirmed persistent acceleration of osteoblast differentiation. Targeted expression of Wdr5 to osteoblasts resulted in earlier activation of the canonical. Wnt signaling pathway in the bone collar as well as in primary calvarial osteoblast cultures. In addition, overexpression of Wdr5 increased the expression of OPG, a target of the canonical Wnt signaling pathway. Overall, our findings suggest that Wdr5 accelerates osteoblast differentiation in association with activation of the canonical Wnt pathway. (c) 2006 Elsevier Inc. All rights reserved.