Pyrophosphate regulatory mechanism in bone mineralization

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08256
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Osaka University
• Principal Investigator: Kubota Takuo 大阪大学, 大学院医学系研究科, 准教授 (40629135)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 骨代謝 / リン酸 / 間葉系幹細胞 / 非古典的Wntシグナル

Outline of Final Research Achievements

Phosphate is an essential mineral for bone formation. However, the mechanism by which phosphate promotes osteogenic differentiation is not fully understood. We induced differentiation of human bone marrow-derived mesenchymal stem cells (MSCs) into osteoblasts using media containing β-glycerophosphate or inorganic phosphate which resulted in different phosphate concentrations. In this study, we found that phosphate upregulates the expression of WNT5b, WNT11, and phosphorylated c-Jun during early differentiation of MSCs into osteoblasts, activates the non-canonical Wnt signaling pathway, and promotes osteogenic differentiation.

Free Research Field

小児科学

Academic Significance and Societal Importance of the Research Achievements

骨の正常な発達・恒常性維持は人間の健康にとって重要であり、骨形成を担う骨芽細胞分化のメカニズムを探ることは、骨形成の生理や代謝性骨疾患の病態の研究に不可欠である。我々は、本研究でリン酸によって誘導される骨芽細胞分化の初期段階における非古典的Wntシグナル伝達経路の活性化の関与について示した。これらの知見は、骨形成分化におけるリン酸と非古典的Wntシグナル伝達経路の関連について新たな視点を提供する。