Review Article

Journal of Bone and Mineral Metabolism

, Volume 27, Issue 3, pp 265-271

First online:

Wnt signaling in bone metabolism

  • Takuo KubotaAffiliated withDepartment of Pediatrics, Osaka University Graduate School of MedicineDepartment of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health Email author 
  • , Toshimi MichigamiAffiliated withDepartment of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health
  • , Keiichi OzonoAffiliated withDepartment of Pediatrics, Osaka University Graduate School of Medicine

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Abstract

A variety of in vivo models have increased understanding of the role of Wnt signaling in bone since mutations in the LRP5 gene were found in human bone disorders. Canonical Wnt signaling encourages mesenchymal progenitor cells to differentiate into osteoblasts. In osteoblasts, Wnt pathway also promotes proliferation and mineralization, while blocks apoptosis and osteoclastogenesis by increasing the OPG/RANKL ratio. Lrp6-mediated signaling in osteoblasts may regulate osteoclastogenesis. However, the role of canonical Wnt signaling in osteoclasts remains unknown, and our understanding of the role of non-canonical Wnt signaling in bone biology is also not sufficient. As to pharmacological intervention, many levels may be considered to target in Wnt signaling pathway, although tumorigenicity and toxicity to other tissues are important. Mesd might be one of target molecules to increase the quantity of LRP5/6 in the plasma membrane. Since sclerostin is almost exclusively expressed in osteocytes, abrogating sclerostin is the most promising design.

Keywords

Wnt signaling LRP5 LRP6 Osteoblast Osteoclast