| Project/Area Number |
16K20657
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthodontics/Pediatric dentistry
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| Research Institution | Nihon University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | Down症候群 / 歯周病 / NF-κB / ユビキチンリガーゼ / PDLIM2 / ダウン症候群 / 口腔細菌 / 遺伝子解析 / 免疫応答 / Porhyromonas gingivalis |
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| Outline of Final Research Achievements |
Individuals with Down syndrome (DS) have a high prevalence of severe periodontitis, which develops early and proceeds rapidly, in comparison with healthy controls (non DS). The abnormal factors in their host responses has been considered to result in severe periodontal disease in individuals with DS. However, the mechanisms of development and procedure of periodontal inflammation in DS have not been fully understood. The nuclear PDZ and LIM domain protein 2 (PDLIM2) is an ubiquitin E3 ligase that targets the p65 subunit of NF-κB, thus terminating NF-κB-mediated inflammation. In this study, we examined the level of PDLIM2 mRNA in the gingival fibroblasts from individuals with DS (DGF) and non DS (NGF). The level of PDLIM2 mRNA expression in DGF was constitutively lower than that in NGF. These data indicate that low level expression of PDLIM2 in DGF may be responsible for the severe periodontal disease in DS patients.
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| Academic Significance and Societal Importance of the Research Achievements |
疾患の病態解明のために，その疾患特有の遺伝子に欠損もしくは変異が生じている遺伝性疾患を利用する手法が用いられている。なかでも近年，早老症であるDown症候群（DS）由来細胞を用いたアルツハイマー病の病態解明が大きな成果をあげている。本研究ではDS由来歯肉線維芽細胞において健常者と比較して炎症を負に制御するPDLIM2の遺伝子発現が恒常的に低い傾向にあることが明らかになった。さらに，その多くが小児DS由来の試料であるため，経過を追うことで将来的な歯周病発症の有無を検討し，DSにおける免疫応答性の個体差を明らかにすることができれば，健常者における歯周病の病態解明にも応用できるものと考えられる。
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