| Project/Area Number |
17K11986
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Periodontology
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
武富 孝治 久留米大学, 医学部, 講師 (10553290)
西村 英紀 九州大学, 歯学研究院, 教授 (80208222)
福田 隆男 九州大学, 大学病院, 講師 (80507781)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Spouty2 / 骨芽細胞 / FGF / BMP / ERK1/2 / Smad1/5/8 / Spry2 / periodontal regeneration / inhibitor / tissue remodeling |
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| Outline of Final Research Achievements |
In this study, we investigated the involvement of Sprouty2 (Spry2) in osteoblast proliferation and differentiation. We examined Spry2 expression in MC3T3-E1 cells, and found that high levels of Spry2 expression were induced by basic FGF stimulation. Overexpression of Spry2 in MC3T3-E1 cells resulted in suppressed proliferation compared with control cells. Sprouty2 negatively regulated the phosphorylation of ERK1/2 after basic FGF stimulation, and of Smad1/5/8 after BMP stimulation. Furthermore, Spry2 suppressed the expression of osterix, alkaline phosphatase, and osteocalcin mRNA, which are markers of osteoblast differentiation. Additionally, Spry2 inhibited osteoblast matrix mineralization. These results suggest that Spry2 is involved in the control of osteoblast proliferation and differentiation by downregulating the FGF-ERK1/2 and BMP-Smad pathways, and suppresses the induction of markers of osteoblast differentiation.
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| Academic Significance and Societal Importance of the Research Achievements |
線維芽細胞増殖因子（FGF）と骨形成タンパク質（BMP）は分裂促進因子活性化蛋白質キナーゼ1/2（ERK1/2）とSmadのシグナル伝達経路を通して骨形成と骨芽細胞活性に関して重要な役割を担っている。SpryファミリーはFGFシグナル経路の細胞内抑制因子であり、哺乳類において４つのオルソログが同定され、特にSpry2は骨形成に関与すると言われている。当研究成果によって解明された骨芽細胞のメカニズムは歯周炎にて失われた歯槽骨を再生する治療法の開発の一助を担うと考えられる。
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