Development of a novel drug for periodontitis based on the characteristics of gingival epithelial cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11843
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Periodontology
• Research Institution: Nihon University
• Principal Investigator: YAMAGUCHI Yoko 日本大学, 歯学部, 助教 (00239922)
• Co-Investigator(Kenkyū-buntansha): 大島 光宏 奥羽大学, 薬学部, 教授 (30194145)
• Research Collaborator: HORIE Masafumi ; SAITO Akira ; KAPPART Kai ; MICKE Patrick ; ÖSTMAN Arne
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 初代培養 / 生体外歯周炎モデル / 歯周炎治療薬 / HGF

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.

Free Research Field

細胞生物学

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。