Development of a novel drug for periodontitis based on the characteristics of gingival epithelial cells
| Project/Area Number |
16K11843
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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 | Nihon University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
大島 光宏 奥羽大学, 薬学部, 教授 (30194145)
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| Research Collaborator |
HORIE Masafumi
SAITO Akira
KAPPART Kai
MICKE Patrick
ÖSTMAN Arne
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 初代培養 / 生体外歯周炎モデル / 歯周炎治療薬 / HGF / 3次元培養 / 初代培養細胞 / 初代培養上皮細胞 / 三次元培養 / コラーゲン分解 / 上皮細胞 |
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| Outline of Final Research Achievements |
Therapeutic agent for periodontitis, in particular, a drug that exerts an effect by applying to gingival epithelium, was searched using periodontitis-causing fibroblasts-containing culture model that we have established. However, no candidate was found that could inhibit the degradation of collagen which connects teeth and bone only by acting on the epithelium.
Therefore, we have re-examined the periodontitis-causing fibroblasts, and found highly expression of hepatocyte growth factor (HGF) during collagen degradation. Using neutralizing antibody to inhibit HGF activity, it was found that the collagen degradation was inhibited in the model and furthermore, improved the clinical indices in monkeys that have naturally-occurred periodontitis.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで細菌が原因と勘違いされてきた歯周炎において、コラーゲン分解能力が極端に高い原因細胞とみられる細胞を取り出すとともに、三次元培養モデルを用いて原因候補となる遺伝子のひとつが肝細胞増殖因子（HGF）であることを突き止めた。このHGFの働きを止める中和抗体の効果をモデルで証明したのち、歯周炎を自然発症したサルの歯肉に注射したところ、その症状が改善した。これらのことから、本研究では世界で初めて歯周炎を抗体によって治療できる可能性を示唆することができた。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] TBX4 is involved in the super-enhancer-driven transcriptional programs underlying features specific to lung fibroblasts.2018
Author(s)
Horie M, Miyashita N, Mikami Y, Noguchi S, Yamauchi Y, Suzukawa M, Fukami T, Ohta K, Asano Y, Sato S, Yamaguchi Y, Ohshima M, Suzuki HI, Saito A, Nagase T.
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Journal Title
Am J Physiol Lung Cell Mol Physiol.
Volume: 314
Issue: 1
Pages: L177-L191
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Integrative CAGE and DNA Methylation Profiling Identify Epigenetically Regulated Genes in NSCLC2017
Author(s)
Horie M, Kaczkowski B, Ohshima M, Matsuzaki H, Noguchi S, Mikami Y, Lizio M, Itoh M, Kawaji H, Lassmann T, Carninci P, Hayashizaki Y, Forrest ARR, Takai D, Yamaguchi Y, Micke P, Saito A, Nagase T.
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Journal Title
Mol Cancer Res.
Volume: 15
Issue: 10
Pages: 1354-1365
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis.2016
Author(s)
Horie M, Yamaguchi Y, Saito A, Nagase T, Lizio M, Itoh M, Kawaji H, Lassmann T, Carninci P, Forrest AR, Hayashizaki Y, Suzutani T, Kappert K, Micke P, Ohshima M.
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Journal Title
Sci Rep
Volume: 6
Issue: 1
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] MicroRNA profiling in gingival crevicular fluid of periodontitis patients.2018
Author(s)
Ohshima M, A. Saito, Horie M, Ejiri K, Aoki A, Katagiri S, Maekawa S, Suzuki S, Kong S, Yamauchi T, Yamaguchi Y, Izumi Y
Organizer
EuroPerio9
Related Report
Int'l Joint Research
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