Regulation of bone minerals by FGF23/klotho axis related to osteocytic function

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390406
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Hokkaido University
• Principal Investigator: AMIZUKA Norio 北海道大学, 歯学研究科(研究院), 教授 (30242431)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 骨細胞 / FGF23 / klotho / 骨基質 / 石灰化

Outline of Final Research Achievements

Signaling linked to αklotho/FGF23 is predominantly found in the proximal renal tubules, where it inhibits Pi reabsorption and 1α-hydroxylase activity. Therefore disrupted function of FGF23/αklotho in kl/kl mice and αklotho-deficient (αklotho-/-) mice results in hyperphosphatemia and hypercalcemia. Despite of elevated concentration of serum Pi, bone minerals around several osteocytes were disappeared. Kl/kl mice fed with low Pi diet showed improved bone matrix, but, αklotho-/- mice still demonstrated patched unmineralized areas in the periphery of the osteocytes. In the kidney of kl/kl mice fed with low Pi diet showed increased expression of αklotho. Therefore, it seems likely that improved histology in bone in kl/kl mice may be due to increased expression of αklotho, but not normalized concentration of serum Pi.

Free Research Field

細胞組織学、骨代謝学