Wdr5 is required for chick skeletal development.
Wdr5 is required for chick skeletal development.
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DOI：
10.1002/jbmr.144
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发表时间：
2010-11
影响因子：
6.2
通讯作者：
Gori, Francesca
中科院分区：
文献类型：
--
作者：
Zhu, Shimei;Zhu, Eric D.;Provot, Sylvain;Gori, Francesca
Wdr 5是属于WD重复蛋白家族的BMP-2诱导蛋白，在生长板的增殖和肥大软骨细胞和成骨细胞中表达。虽然以前的研究提供了深入了解Wdr 5影响软骨细胞和成骨细胞分化的机制，Wdr 5在体内是否是软骨内骨发育所必需的尚未解决。在这些研究中，使用禽复制型逆转录病毒（RCAS）系统提供Wdr 5短发夹（sh）RNA沉默Wdr 5在发展中的肢体，我们报告说，减少Wdr 5水平延迟软骨内骨发育，从而导致骨骼元素的缩短。骨骼元素的缩短是由于受损的软骨细胞成熟，证明了显着减少Runx-2，X型胶原和骨桥蛋白的表达。当Wdr 5水平降低时，也观察到成骨细胞中Runx-2、I型胶原和骨桥蛋白表达的减少以及矿化骨的随后缺损。最重要的是，Runx-2的逆转录病毒错误表达挽救了Wdr 5 shRNA诱导的表型。这些研究结果表明，在肢体发育过程中，Wdr 5所需的软骨内骨形成和Wdr 5影响这一进程，至少部分，通过调节Runx-2的表达。
Wdr5, a BMP-2 induced protein belonging to the family of the WD repeat proteins, is expressed in proliferating and hypertrophic chondrocytes of the growth plate and in osteoblasts. Although previous studies have provided insight into the mechanisms by which Wdr5 affects chondrocyte and osteoblast differentiation, whether Wdr5 in vivo is required for endochondral bone development has not been addressed. In these studies, using an avian replication competent retrovirus (RCAS) system delivering Wdr5 short hairpin (sh) RNA to silence Wdr5 in the developing limb, we report that reduction of Wdr5 levels delays endochondral bone development and consequently results in shortening of the skeletal elements. Shortening of the skeletal elements was due to impaired chondrocyte maturation, evidenced by a significant reduction of Runx-2, type X collagen and osteopontin expression. A decrease in Runx-2, type collagen I and ostepontin expression in osteoblasts and subsequent defect in mineralized bone was observed as well when Wdr5 levels were reduced. Most importantly, retroviral misexpression of Runx-2 rescued the phenotype induced by Wdr5 shRNA. These findings suggest that during limb development Wdr5 is required for endochondral bone formation and that Wdr5 influences this process, at least in part, by regulating Runx-2 expression.
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影响因子：
4.8
作者：
Gori, F;Demay, MB
通讯作者：
Demay, MB
影响因子：
2.7
作者：
Gori, Francesca;Friedman, Lauren G.;Demay, Marie B.
通讯作者：
Demay, Marie B.
影响因子：
2.6
作者：
Duprez, D;Bella, EJD;FrancisWest, PH
通讯作者：
FrancisWest, PH
影响因子：
4.6
作者：
Hashimoto, Takao;Zhang, Xiang-Mei;Yang, Xian-Jie
通讯作者：
Yang, Xian-Jie
RCAS-RNAI：一种发育中的鸡视网膜的功能丧失方法。
影响因子：
--
作者：
Harpavat, S;Cepko, CL
通讯作者：
Cepko, CL