Role of Osteocytes in Phosphate Sensing and Its Relation to Skeletal Maturation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07838
• 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: Osama Woman's and Children's Hospital
• Principal Investigator: Michigami Toshimi 地方独立行政法人大阪府立病院機構大阪母子医療センター(研究所), 骨発育疾患研究部門(旧環境影響部門), 部長 (00301804)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: リン代謝 / 骨細胞 / 骨芽細胞分化 / 骨成熟

Outline of Final Research Achievements

Using mouse models, we have investigated the relation between the skeletal maturation and alteration in phosphate metabolism during growth period. The bones of adult mice contained more abundant FGF23 protein than those of young mice. However, the expression of other analyzed molecules related to phosphate metabolism and osteoblastic differentiation was stronger in the osteoblasts and osteocytes derived from young mice than those from adult mice, and they were also up-regulated in the osteoblasts and osteocytes from a mouse model of hypophosphatemic rickets. The renal expression of Cyp24a1 was lower, and that of Slc34a3 was higher, in the younger mice than in the adult mice, which might suggest a weaker action of FGF23 and might contribute to the increase of phosphate in the body during growth period.

Free Research Field

骨ミネラル代謝学、小児科学

Academic Significance and Societal Importance of the Research Achievements

成長期にはリンの需要が高まり、リンの不足はくる病などの代謝性骨疾患や成長障害をきたすため、小児医療においてリン代謝の理解は重要である。本研究により、成長に伴って骨芽細胞や骨細胞におけるリン代謝や石灰化に関わる分子群の発現やリン酸応答性が変化することが明らかになった。また、低リンくる病の病態形成に骨芽細胞・骨細胞の成熟障害が関連していることが示唆された。