| Project/Area Number |
18K09047
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 56020:Orthopedics-related
|
|---|
| Research Institution | Tokyo Dental College |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
小野寺 晶子 東京歯科大学, 歯学部, 講師 (90637662)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | Runx2 / アルカリホスファターゼ / 骨芽細胞分化 / 細胞核機能制御 / 骨芽細胞 / 転写制御 / 遺伝子発現制御 |
|---|
| Outline of Final Research Achievements |
Tissue-nonspecific alkaline phosphatase (TNAP) promotes hydroxyapatite crystal formation by degrading inorganic pyrophosphate (PPi) and increasing inorganic phosphate (Pi) concentration. However, abnormalities in Alpl KO mouse-derived osteoblasts are poorly understood. Therefore, in this study, we aimed to investigate the precise role of TNAP in osteoblast differentiation. TNAP inhibition by levamisole, a reversible TNAP inhibitor, suppressed the osteoblast differentiation. Alpl overexpression increased the expression of Runx2, Sp7, Bglap2 and Dmp1 in Alpl KO cells. TNAP regulated Runx2 expression, which in turn regulated the expression of all other osteoblast markers, except Dmp1. Dmp1 expression was independent of RUNX2 but was dependent on extracellular Pi concentration in Runx2-deficient osteogenic cells. These results suggest that TNAP functions as an osteogenic differenti- ation regulator either by regulating Runx2 expression or by controlling extracellular Pi concentration.
|
| Academic Significance and Societal Importance of the Research Achievements |
超高齢化社会を迎えた我が国では骨粗鬆症などの骨疾患患者数の増加が問題となっており、これに対する新たな予防法・治療法の開発が求められている。本研究ではアルカリホスファターゼが骨形成を直接促進する因子である事が明らかとなったことから、アルカリホスファターゼを標的とした硬組織疾患に対する新規予防法・治療法の開発が期待できる。
|
