| Project/Area Number |
19K18989
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 57030:Conservative dentistry-related
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
MAEKAWA Shogo 東京医科歯科大学, 歯学部, 非常勤講師 (20793574)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 歯周炎 / S100A8 / Catepthin K / RNA sequencing / DAMPs / RNA-seq / 結紮誘導歯周炎 / NGS / 急速な歯周組織破壊 / S100A9 |
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| Outline of Research at the Start |
本研究では、PAMPsの影響のない無菌マウスを用いて咬合性外傷や結紮によってDAMPsが誘発されるか、また歯周組織に与えるDAMPsの生物学的影響に関して、NGSを用いて網羅的な解析を行う。さらに通常のマウスと比較を行い、PAMPs影響下におけるDAMPsの働きに関して解析を行うことで、現在の咬合性外傷に対するコンセンサスに生物学的な根拠を追加できるよう模索する。
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| Outline of Final Research Achievements |
Comprehensive genetic analysis of inflamed gingival tissues with ligature-induced periodontitis showing rapid periodontal tissue destruction revealed enhanced innate immune response and increased cellular response to stress. The expression of S100A8 and S100A9, which are damage-associated molecular patterns (DAMPs), and MMP9 and cathepsin K, which are related to bone resorption, were significantly increased in ligated gingival tissues. In addition, increased expression of S100A8 and S100A9 was observed in ligature-induced periodontitis, and eventually their expression was infiltrated into connective tissue. Experiments using an oral-derived human epithelial cell line (Ca9-22) showed that S100A8 and S100A9 were involved in the expression of cathepsin K. This study elucidated a part of the rapid destruction of periodontal tissues by DAMPs.
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| Academic Significance and Societal Importance of the Research Achievements |
超高齢社会となった日本だけでなく、世界においても高齢化が進んでおり、また歯周病の罹患率も現在に至る約30年間増加している。歯周炎は主な歯の喪失原因であり、長期にわたる健康的な口腔内環境の確立と維持、疾病予防のためにも、歯周組織破壊のメカニズム解明は重要である。今回、急速な歯周組織破壊を呈する歯周炎モデルから傷害関連分子パターンであるS100A8やS100A9のカテプシンKへの関与、骨吸収に関わるメカニズムの一端を解明することができた。今後の歯周炎の予防、治療に応用することが期待される。
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