| Project/Area Number |
18H02964
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 57010:Oral biological science-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
AMIZUKA Norio 北海道大学, 歯学研究院, 教授 (30242431)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Keywords | 石灰化 / リン酸供与膜輸送体 / 副甲状腺ホルモン / 骨芽細胞 / 微細構造 |
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| Outline of Final Research Achievements |
The purpose of this study is to evaluate if the synthesis and supply of phosphate ions －a constituent of calcified bone matrix－ is regulated by serum concentration of parathyroid hormone (PTH). PTH-administered mice showed the increased expression of TNAP, ENPP1, ANK, PHOSPHO1 and SIBLING family, consequently resulting in highly-calcified bone matrix. In contrast, NaPiIIa/IIc mice bearing hypophosphatemia revealed no change of TNAP, ENPP1, ANK, PHOSPHO1 genes and SIBLING family, showing less amount of bone volume. Hyp mice － another hypophosphatemia model due to mutation in Phex－demonstrated huge areas of uncalcified bone matrix. Taken together, it seems likely that PTH increases the synthesis and supply of phosphate ions in bone, while calcification in bone matrix is regulated by Phex/SIBLING family.
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| Academic Significance and Societal Importance of the Research Achievements |
超高齢化社会を迎えた現在、骨をはじめとする運動器の健康維持はヒトの健康寿命を延ばすうえで大きく貢献すると思われる。特に、骨強度に深く関与する骨基質石灰化は、血清カルシウム(Ca)とリンによって規定されると考えられているが、血清Ca濃度はほぼ一定に維持されていることから、血清リン濃度変化による骨基質石灰化が注目を浴びている。特に、骨基質石灰化において、骨代謝に影響を与える副甲状腺ホルモンによるリン酸供与作用の検索は、基礎研究から骨基質石灰化のメカニズムを解明することに繋がり、正常あるいは病的石灰化において重要な情報を与えると考えられる。
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