Tamura Masato, Nemoto Eiji, Sato Mari M, Nakashima Aiko, Shimauchi Hidetoshi
Department of Biochemistry and Molecular Biology, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
Front Biosci (Elite Ed). 2010 Jun 1;2(4):1405-13. doi: 10.2741/e201.
Signaling by the Wnt plays a central role in many processes during embryonic development and adult homeostasis. At least 19 types of Wnts, several families of secreted antagonists and multiple receptors have been identified. Two distinct Wnt signaling pathways, the canonical pathway and the noncanonical pathway have been described. Functional studies and experimental analysis of relevant animal models confirmed the effects of Wnt on regulation of developing mineralized tissue formation and adult homeostasis. In osteoblasts, the canonical Wnt pathway modulates differentiation, proliferation and mineralization, while it blocks apoptosis and osteoclastogenesis by increasing osteoprotegerin. Functional crosstalk between Wnt and bone morphogenetic protein signaling during osteoblastic differentiation has been reported. Recently, non-canonical Wnt signaling was shown to play a role in bone formation. The Wnt signaling pathway also plays an important role not only in tooth formation but also in differentiation and proliferation of cementoblasts and odontoblasts in the tooth. This present review provides an overview of progress in elucidating the role of Wnt signaling pathways in bone and tooth and the resulting possibilities for therapeutic potential.
Wnt信号传导在胚胎发育和成年期体内平衡的许多过程中起着核心作用。现已鉴定出至少19种类型的Wnt、几个分泌型拮抗剂家族和多种受体。已描述了两种不同的Wnt信号传导途径,即经典途径和非经典途径。相关动物模型的功能研究和实验分析证实了Wnt对发育中矿化组织形成调节和成年期体内平衡的影响。在成骨细胞中,经典Wnt途径调节分化、增殖和矿化,同时通过增加骨保护素阻断细胞凋亡和破骨细胞生成。已有报道称在成骨细胞分化过程中Wnt与骨形态发生蛋白信号传导之间存在功能性串扰。最近,非经典Wnt信号传导被证明在骨形成中起作用。Wnt信号传导途径不仅在牙齿形成中,而且在牙齿中牙骨质细胞和成牙本质细胞的分化和增殖中也起着重要作用。本综述概述了在阐明Wnt信号传导途径在骨骼和牙齿中的作用方面取得的进展以及由此产生的治疗潜力可能性。
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