Duan Peipei, Bonewald L F
State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri-Kansas City, Kansas City, MO, USA.
Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri-Kansas City, Kansas City, MO, USA.
Int J Biochem Cell Biol. 2016 Aug;77(Pt A):23-29. doi: 10.1016/j.biocel.2016.05.015. Epub 2016 May 19.
The Wnt signaling pathway is known as one of the important molecular cascades that regulate cell fate throughout lifespan. The Wnt signaling pathway is further separated into the canonical signaling pathway that depends on the function of β-catenin (Wnt/β-catenin pathway) and the noncanonical pathways that operate independently of β-catenin (planar cell polarity pathway and Wnt/Ca(2+) pathway). The Wnt/β-catenin signaling pathway is complex and consists of numerous receptors, inhibitors, activators, modulators, phosphatases, kinases and other components. However, there is one central, critical molecule to this pathway, β-catenin. While there are at least 3 receptors, LRP 4, 5 and 6, and over twenty activators known as the wnts, and several inhibitors such as sclerostin, dickkopf and secreted frizzled-related protein, these all target β-catenin. These regulators/modulators function to target β-catenin either to the proteasome for degradation or to the nucleus to regulate gene expression. Therefore, the interaction of β-catenin with different factors and Wnt/β-catenin signaling pathway will be the subject of this review with a focus on how this pathway relates to and functions in the formation and maintenance of bone and teeth based on mainly basic and pre-clinical research. Also in this review, the role of this pathway in osteocytes, bone cells embedded in the mineralized matrix, is covered in depth. This pathway is not only important in mineralized tissue growth and development, but for modulation of the skeleton in response to loading and unloading and the viability and health of the adult and aging skeleton.
Wnt信号通路是已知的在整个生命周期中调节细胞命运的重要分子级联反应之一。Wnt信号通路进一步分为依赖于β-连环蛋白功能的经典信号通路（Wnt/β-连环蛋白通路）和独立于β-连环蛋白运作的非经典通路（平面细胞极性通路和Wnt/Ca(2+)通路）。Wnt/β-连环蛋白信号通路很复杂，由众多受体、抑制剂、激活剂、调节剂、磷酸酶、激酶和其他成分组成。然而，该通路有一个核心关键分子，即β-连环蛋白。虽然已知至少有3种受体，即低密度脂蛋白受体相关蛋白4、5和6，以及20多种被称为Wnts的激活剂，还有几种抑制剂，如硬化蛋白、Dickkopf和分泌型卷曲相关蛋白，但这些都以β-连环蛋白为靶点。这些调节因子/调节剂的作用是将β-连环蛋白靶向蛋白酶体进行降解或靶向细胞核以调节基因表达。因此，β-连环蛋白与不同因子的相互作用以及Wnt/β-连环蛋白信号通路将是本综述的主题，重点是基于主要的基础研究和临床前研究，该通路在骨骼和牙齿的形成与维持中如何发挥作用以及其功能。此外，本综述还深入探讨了该通路在骨细胞（嵌入矿化基质中的骨细胞）中的作用。该通路不仅在矿化组织的生长和发育中很重要，而且对于响应加载和卸载调节骨骼以及成年和衰老骨骼的活力与健康也很重要。
