Wnt regulation of chondrocyte differentiation
Wnt regulation of chondrocyte differentiation
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DOI：
10.1242/jcs.00152
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发表时间：
2002-12-15
影响因子：
4
通讯作者：
Francis-West, P
中科院分区：
文献类型：
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作者：
Church, V;Nohno, T;Francis-West, P
Wnt家族的生长因子是包括骨骼发生在内的多种发育过程的重要调节因子。为了进一步研究Wnt的作用，我们分析了它们在发育中的鸡肢中的表达，并在体内和体外进行了功能分析。我们发现，Wnt5b和Wnt11被限制在软骨元件的prehypertrophic软骨细胞内，Wnt5a被发现在关节和软骨膜中，而Wnt4在发育中的关节中表达，在一些骨骼中，是肥大软骨细胞的一个子集。这些Wnt在体外和体内介导对软骨形成和软骨细胞分化的启动的不同作用。Wnt4阻断软骨形成的起始并促进终末软骨细胞的体外分化。相反，Wnt5a和Wnt5b在体外促进早期软骨形成，同时在体内抑制终末分化。由于Wnt5b和Wnt11的表达与印度刺猬（Ihh）重叠并出现在Ihh之后，我们还将它们的作用与Ihh进行了比较，以了解它们是否介导Ihh信号传导的各个方面。这表明Ihh和Wnt5b和Wnt11以平行途径控制软骨形成。
The Wnt family of growth factors are important regulators of several developmental processes including skeletogenesis. To further investigate the role of Wnts we analysed their expression in the developing chick limb and performed functional analyses in vivo and in vitro. We found that Wnt5b and Wnt11 are restricted within the prehypertrophic chondrocytes of the cartilage elements, Wnt5a is found in the joints and perichondrium, while Wnt4 is expressed in the developing joints and, in some bones, a subset of the hypertrophic chondrocytes. These Wnts mediate distinct effects on the initiation of chondrogenesis and differentiation of chondrocytes in vitro and in vivo. Wnt4 blocks the initiation of chondrogenesis and accelerates terminal chondrocyte differentiation in vitro. In contrast, Wnt5a and Wnt5b promote early chondrogenesis in vitro while inhibiting terminal differentiation in vivo. As Wnt5b and Wnt11 expression overlaps with and appears after Indian hedgehog (Ihh), we also compared their effects with Ihh to see if they mediate aspects of Ihh signalling. This showed that Ihh and Wnt5b and Wnt11 control chondrogenesis in parallel pathways.