Study on the FGF23 metabolic regulation mechanism derived bone as a novel phosphaturic factor in renal insufficient status.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09652
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Wakayama Medical University
• Principal Investigator: Shigematsu Takashi 和歌山県立医科大学, 医学部, 教授 (30187348)
• Co-Investigator(Kenkyū-buntansha): 大矢 昌樹 和歌山県立医科大学, 医学部, 講師 (90550301)
• Project Period (FY): 2016-10-21 – 2019-03-31
• Keywords: FGF23 / 骨細胞 / 骨芽細胞 / ビタミンD / リン

Outline of Final Research Achievements

We estimated the FGF23 production in vitro among isolated osteoblasts, osteocytes and osteoclast in bone constitution cells without osteocyte harvest. The osteoblastic Cell Line MC3T3-E1 cells have ability to be calcified spontaneously. We changed these cells into osteocytes by ascorbic acid and phosphate overload in vitro. We estimate the FGF23 mRNA expression at each stage from osteoblast to osteocyte. The both of matured osteoblast and immature osteocyte had the most effective production ability. We discovered that the most powerful stimulator on FGF23 is active vitamin D and analogues (vitamin D receptor activator), but not phosphate loading.
In addition, we were able to observe the even plasmatoid dendritic cell in spleen and calcified vessel as an ectopic calcification have also FGF23 production ability. These phenomena might explain the effect of FGF23 on cardiovascular events and immune system. This area is needed further investigation.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

FGF23は腎機能障害者においては、生命予後と密接に関係することが明らかとなりつつある。またFGF23受容体となるKlotho蛋白をコードするKlotho遺伝子は長寿遺伝子すなわち抗老化作用を有することが明らかとなった。
本研究成果は、この老化の本質的なメカニズムの一端を明らかにするものであり、今後の抗老化作用を有する創薬にもつながる成果である。さらには心血管病の進展や免疫系への作用など広い分野の研究領域を啓く可能性がある。