Feasibility study of developing bone formative drugs with regulating Wnt signaling.

• Project/Area Number: 22790510
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Applied pharmacology
• Research Institution: The University of Tokyo
• Principal Investigator: MIURA Shogo 東京大学, 医学部・附属病院, 特任助教 (90529182)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: シグナル伝達 / 発現制御 / 生体分子 / 骨粗鬆症 / 骨芽細胞 / 骨形成 / Wnt / LRP5/6 / Wnt-βcateninシグナル

Research Abstract

Wnt/Fzd signaling has been believed to play a critical role inosteoblast differentiation although the detailed manner was not obviously clarified. In this study, it has been revealed that not only the activation ofβ-catenin pathway, an already known critical pathway, but also the suppression of JNK pathway contributes to osteoblast differentiation. The balance of the activation of these two pathways is likely to be regulated by the quantity of LRP molecules available to form a complex with Wnt ligands. It is also suggested that Wnt molecules regulate subcellular localization of LRP. The relationship between Wnt signaling and LRP subcellular behavior may be a promising clue to elucidate the mystery of Wnt signaling in osteoblast differentiation.