Analysis of regulatory mechanisms of Wnt signaling in bone formation

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K18009
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Saitama Medical University
• Principal Investigator: Tsukamoto Sho 埼玉医科大学, 医学部, 助教 (20707658)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 骨形成 / Wnt / シグナル伝達 / 骨系統疾患

Outline of Final Research Achievements

Wnt proteins stimulates bone formation. It is still unclear which Wnt ligands are important for bone formation, because the 19 different types of Wnt are identified in mammal. Recently, our group found that bone formation was enhanced in Smad4 conditional knockout mice through an increase in the expression of Wnt7b. We established tamoxifen-inducible Wnt7b conditional knockout (Wnt7b cKO). The juvenile Wnt7b cKO mice were small and showed dwarfism phenotypes. Bone analysis revealed that bone length in Wnt7b cKO mice was shorter than that of control mice. Histological sections of long bones revealed that the volume of trabecular bones were decreased in Wnt7b cKO mice compared to the control mice. These results suggest that Wnt7b is a critical inducer of bone formation during endochondral ossification.

Free Research Field

病態生理学

Academic Significance and Societal Importance of the Research Achievements

本研究から、Wnt7bが生理的な骨形成を亢進する重要な因子である可能性を見出した。実際に、Wnt7bは、骨形成を担う骨芽細胞の分化を促進したことから、Wnt7bを介したシグナルが骨粗鬆症等の骨疾患の新たな治療標的となる可能性がある。