Evc works in chondrocytes and osteoblasts to regulate multiple aspects of growth plate development in the appendicular skeleton and cranial base
Evc works in chondrocytes and osteoblasts to regulate multiple aspects of growth plate development in the appendicular skeleton and cranial base
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DOI：
10.1016/j.bone.2011.08.025
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发表时间：
2012-01-01
期刊：
影响因子：
4.1
通讯作者：
Ruiz-Perez, Victor L.
中科院分区：
文献类型：
--
作者：
Pacheco, Maria;Valencia, Maria;Ruiz-Perez, Victor L.
Ellis-van Creveld综合征蛋白同源物（Evc）先前被证明介导软骨细胞中印度hedgehog （Ihh）下游靶点的表达。因此，在Evc（-/-）小鼠中证实了Ihh/Pthrp轴的破坏，但Evc参与软骨内发育的全部程度尚未完全确定。在此，我们在均匀遗传背景下进一步研究了Evc（-/-）生长板，并表明Evc促进软骨膜中软骨细胞增殖、软骨细胞肥大和成骨细胞分化，从而暗示Evc具有pthrp依赖性和pthrp非依赖性Ihh功能。我们还证明，定位于成骨细胞初级纤毛的Evc介导成骨细胞谱系中的Hedgehog （Hh）信号传导。尽管如此，骨颈发育在Evc（-/-）突变体中受到轻微影响。在Evc（-/-）小鼠软骨内成骨的初始阶段，成骨细胞标志物和Wnt/ β -连环蛋白信号成分的表达前沿位于Evc（-/-）软骨膜的初级海绵附近，这是由于成骨细胞分化受损。此外，我们使用Ptch1-LacZ报告小鼠来了解存在于正常和Evc（-/-）小鼠软骨膜中的不同类型的hh反应细胞。Evc在软骨膜内细胞中介导Hh靶基因的表达，但在软骨膜外细胞中是不可缺少的。最后，我们报道了Evc（-/-）小鼠的颅底缺陷，并揭示Evc对椎体内软骨联合症的发展至关重要。(C) 2011出版的爱思唯尔公司。
Ellis-van Creveld syndrome protein homolog (Evc) was previously shown to mediate expression of Indian hedgehog (Ihh) downstream targets in chondrocytes. Consequently disruption of the Ihh/Pthrp axis was demonstrated in Evc(-/-) mice, but the full extent of Evc involvement in endochondral development was not totally characterized. Herein we have examined further the Evc(-/-) growth plate in a homogeneous genetic background and show that Evc promotes chondrocyte proliferation, chondrocyte hypertrophy and the differentiation of osteoblasts in the perichondrium, hence implicating Evc in both Pthrp-dependent and Pthrp-independent Ihh functions. We also demonstrate that Evc, which localizes to osteoblast primary cilia, mediates Hedgehog (Hh) signaling in the osteoblast lineage. In spite of this, bone collar development is mildly affected in Evc(-/-) mutants. The onset of perichondrial osteoblastogenesis is delayed at the initial stages of endochondral ossification in Evc(-/-) mice, and in later stages, the leading edge of expression of osteoblast markers and Wnt/beta-catenin signaling components is located closer to the primary spongiosa in the Evc(-/-) perichondrium owing to impaired osteoblast differentiation. Additionally we have used Ptch1-LacZ reporter mice to learn about the different types of Hh-responsive cells that are present in the perichondrium of normal and Evc(-/-) mice. Evc mediates Hh target gene expression in inner perichondrial cells, but it is dispensable in the external layers of the perichondrium. Finally, we report cranial base defects in Evc(-/-) mice and reveal that Evc is essential for intrasphenoidal synchondrosis development. (C) 2011 Published by Elsevier Inc.