[Frontiers in Bioscience E2, 1405-1413, June 1, 2010]

Role of the Wnt signaling pathway in bone and tooth

Masato Tamura 1, Eiji Nemoto2, Mari M. Sato1, Aiko Nakashima1, Hidetoshi Shimauchi2

1Department of Biochemistry and Molecular Biology, Graduate School of Dental Medicine, Hokkaido University, N13, W7, Sapporo, Japan, 2Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba, Sendai, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. The Wnt signaling pathway
4. The Canonical Wnt signaling pathway and bone
4.1. LRP5
4.2. beta-catenin
4.3. Osteoblasts
4.4. Crosstalk between canonical Wnt and BMP signaling
4.5. Sost
5. Non-canonical Wnt signaling and bone
6. Wnt signaling and bone disease
7. Wnt signaling in the tooth
8. Therapeutic potential and prospective
9. References

1. ABSTRACT

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.