Analysis of the regulatory mechanism of bone and tooth homeostasis by glucocorticoids.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K18465
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Showa University
• Principal Investigator: Azetsu Yuki 昭和大学, 歯学部, 助教 (00812190)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: グルココルチコイド / 骨芽細胞 / 破骨細胞 / メダカ / マウス / FK506 / 修復 / 再生

Outline of Final Research Achievements

Synthetic Glucocorticoid (GC) cause adverse effects on bone metabolism and pose potential risks to tooth development. However, the role of GCs in bone metabolism under physiological conditions is still not well understood. We generated glucocorticoid receptor 1 (GR1), GR2 and mineralocorticoid receptor (MR)-triple deficient medaka, and revealed that GR and MR regulate the fracture healing through the control of osteoblast accumulation and osteoclast recruitment. Furthermore, since the involvement of GCs in FK506 signaling was suggested, we examined the effects of FK506 on bone repair and osteoblast function. We administered FK506 to the fin regeneration model medaka and the bone defected repair model mouse and found that FK506 promotes bone regeneration and repair.

Free Research Field

骨代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究では、GRとMRの両方が骨折修復に対して抑制的に機能することを明らかにした。これはGC製剤が両受容体を介して骨代謝に作用することを示唆しており、詳細な作用機序を解明することで、GC製剤による治療中でも骨への悪影響を選択的に緩和できる薬剤の開発に大きく貢献できる可能性がある。また、FK506の骨に及ぼす詳細なメカニズムを解明することで、骨再生・修復を促進する新しい薬の開発が期待される。