Research of Exacerbation Factor Cot/ tpl2 as Molecular Target of Periodontitis Treatment
| Project/Area Number |
25462895
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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 |
Functional basic dentistry
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| Research Institution | Kagoshima University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
松口 徹也 鹿児島大学, 医歯学域歯学系, 教授 (10303629)
大西 智和 鹿児島大学, 医歯学域歯学系, 准教授 (30244247)
坂東 健二郎 明海大学, 歯学部, 講師 (50347093)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | Cot/Tpl2 / 歯周病 / シグナル分子 / LPS / 増悪因子 / 発現調節 / MAP3K / NF-kB / マウスモデル / DUSP16 / JNK / expression / periodontitis / mouse model / IL-12p40 / MCPIP-1 / 3'-UTR / mRNA stability |
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| Outline of Final Research Achievements |
MAP3K8/Cot/Tpl2 is serine/threonine kinase and signaling molecule which controls cytokines production in antigen presenting cells (APC). We previously reported that mouse model of periodontitis using WT mice and Cot/Tpl2 knockout mice. It showed that alveolar bone absorption of KO mice is lower than WT mice. It suggests the difference of sensitivity to LPS in both mice. LPS induced mRNA expression of Cot/Tpl2 in 2h and decreased slowly. mRNA expression was inhibited by NF-kB inhibitor MG-132. Promoter assay suggested that -230～-50 promoter region containing three NF-kB binding sites is important for LPS-induced Cot/Tpl2 mRNA expression. In conclusion, Cot/Tpl2 mRNA expression is induced through NF-kB signal pathway.
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| Academic Significance and Societal Importance of the Research Achievements |
歯周病の治療薬は多くの研究がなされているが、いまだ決定的なものはない。我々は以前歯周病マウスモデルを、細胞内シグナル分子、Cot/Tpl2（MAP3K)のノックアウトマウスで作成し、Cot/Tpl2が歯周病増悪因子であることを明らかにした。今回の研究ではLPS（歯周病菌体成分）の刺激により、リン酸化によりシグナルを伝達するCot/Tpl2が、それ自身の発現量を増大することを明らかにした。Cot/Tpl2のの増大が生じる細胞や、歯周病に与える影響を調べることで、Cot/Tpl2をターゲットとした歯周病治療薬、歯周病予防薬などの開発の突破口を開くものと期待される。
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Report
(4 results)
Research Products
(10 results)
