Identification of the bone Klotho-mediated regulation of mineral metabolism

• Project/Area Number: 17K09738
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Tokai University
• Principal Investigator: FUKAGAWA Masafumi 東海大学, 医学部, 教授 (00211516)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 骨細胞 / FGF23 / Klotho / 骨代謝 / 骨ミネラル代謝

Outline of Final Research Achievements

The mechanisms through which the FGF receptor regulates FGF23 synthesis in osteocytes is unknown. To test the hypothesis that Klotho is involved in this process as a coreceptor for the FGF receptor, we generated mice with bone-specific Klotho overexpression. These mice showed markedly increased FGF23 synthesis, presumably through a positive autocrine feedback loop. However, almost all mice died at day 2 or 3, making it difficult to determine the long-term impact on bone metabolism.

Academic Significance and Societal Importance of the Research Achievements

今回の検討結果より，Klothoが骨細胞におけるFGF23分泌制御に深く関与していることが明らかとなった。FGF23はリン代謝，ビタミンD代謝において中心的な役割を担う重要な因子である。本研究成果はFGF23の分泌制御の理解を大きく前進させるものであり，腎臓病に代表されるリン代謝異常の新たな治療薬の開発につながると期待される。