| Project/Area Number |
24592817
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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 | Showa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TAKAMI Masamichi 昭和大学, 歯学部, 教授 (80307058)
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| Co-Investigator(Renkei-kenkyūsha) |
IMAMURA Takahisa 熊本大学, 大学院生命科学研究部, 准教授 (20176499)
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| Research Collaborator |
AKIYAMA Tomohito 昭和大学, 歯学部, 助教 (90710319)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 歯周病 / 破骨細胞 / プロテアーゼ / 骨代謝 / ジンジパイン / 骨 / タンパク質分解酵素 |
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| Outline of Final Research Achievements |
Periodontitis is a chronic inflammatory disease accompanied by alveolar bone loss. Porphyromonas gingivalis, which plays a key role in the etiology of periodontitis, produces cysteine proteases called gingipains. Gingipains are classified into two groups based on their cleavage site specificity, i.e., Rgp
and Kgp. We found that osteoclast differentiation induced by inflammatory cytokines such as TNF-α and IL-1β in co-cultures of mouse osteoblasts and bone marrow cells, whereas RgpB had no effect on osteoclast differentiation under the same experimental conditions. Osteoprotegerin (OPG), a protein that negatively regulates osteoclast differentiation, was degraded by Kgp. Kgp primarily cleaved death-domain-like region of OPG; the fragments containing RANKL-biding domain lost its binding capacity to RANKL. Our data suggests that degradation of OPG by Kgp is a crucial event in the progression of osteolysis in periodontitis.
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