Wnt signaling in cartilage development and diseases: lessons from animal studies.
Wnt signaling in cartilage development and diseases: lessons from animal studies.
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DOI：
10.1038/labinvest.2015.142
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发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Enomoto-Iwamoto M
中科院分区：
文献类型：
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作者：
Usami Y;Gunawardena AT;Iwamoto M;Enomoto-Iwamoto M
软骨不仅在产前和产后的骨骼发育和生长中起着至关重要的作用，而且在整个生命过程中为骨骼的平稳运动提供服务。因此，软骨功能障碍引起各种骨骼疾病。动物实验结果表明，依赖β-catenin的典型和独立的非典型Wnt信号通路在调节软骨发育、生长和维持中具有多种作用。β-catenin依赖的信号是软骨内成骨和轴尾骨骼生长所必需的，而该信号的过度激活会严重抑制小鼠软骨的初始形成和生长板的组织和功能。相反，非典型Wnt信号在生长板软骨细胞的柱状组织中很重要。在啮齿动物骨关节炎模型中，操纵Wnt信号导致或改善关节软骨退变。人类遗传学研究表明，Wnt/β-catenin信号是骨关节炎的一个危险因素。Wnt信号分子的表达分析和体内、体外功能实验的累积结果表明，Wnt信号是骨关节炎的治疗靶点。Wnt信号的靶组织不仅可能是关节软骨，也可能是滑膜和软骨下骨。
Cartilage not only plays essential roles in skeletal development and growth during pre-and post-natal stages but also serves to provide smooth movement of skeletons throughout life. Thus dysfunction of cartilage causes a variety of skeletal disorders. Results from animal studies reveal that β-catenin-dependent canonical and independent non-canonical Wnt signaling pathways have multiple roles in regulation of cartilage development, growth and maintenance. β-catenin-dependent signaling is required for progression of endochondral ossification and growth of axial and appendicular skeletons while excessive activation of this signaling can cause severe inhibition of initial cartilage formation and growth plate organization and function in mice. In contrast, non-canonical Wnt signaling is important in columnar organization of growth plate chondrocytes. Manipulation of Wnt signaling causes or ameliorates articular cartilage degeneration in rodent osteoarthritis models. Human genetic studies indicate that Wnt/β-catenin signaling is a risk factor for osteoarthritis. Accumulative findings from analysis of expression of Wnt signaling molecules and in vivo and in vitro functional experiments suggest that Wnt signaling is a therapeutic target for osteoarthritis. The target tissues of Wnt signaling may be not only articular cartilage but also synovium and subchondral bone.