Elucidation of the mechanisms of PHT and NIF induced gingival overgrowth

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K17070
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57030:Conservative dentistry-related
• Research Institution: Hiroshima University
• Principal Investigator: OKANOBU AI 広島大学, 医系科学研究科(歯), 助教 (00806581)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 薬物性歯肉増殖症 / マウスモデル / フェニトイン / ニフェジピン

Outline of Final Research Achievements

The applicant conducted a study to investigate whether NR4A1 is a central mechanism of drug induced gingival overgrowth in the model of phenytoin (PHT) and nifedipine (NIF) induced gingival overgrowth. First, to establish PHT and NIF induced gingival overgrowth mice model, we conducted experiments at various concentrations, dosing methods, and dosing times, but did not develop prominent overgrowth. So, PHT and NIF and the effect of NR4A1 on gingival overgrowth was investigated in vitro. As a result, it was shown that in human gingival fibroblasts, NIF and PHT suppress the nuclear translocation of NFATc3 and also suppress the expression of NR4A1, resulting in the enhanced expression of type I collagen.

Free Research Field

歯周病学

Academic Significance and Societal Importance of the Research Achievements

本研究は申請者が過去に実施してきたCsA誘導性歯肉増殖症の研究成果をもとに、PHT、NIFで誘導された歯肉増殖症モデルを作製し、NR4A1が薬物性歯肉増殖症メカニズムの中心的な役割を持つ分子であるかを調べることを目的としている。本研究のNR4A1を中心としたメカニズムの解明は、新規治療法や予防法の開発につながり、薬剤変更や外科処置が困難な患者、口腔衛生管理が困難な超高齢の薬物性歯肉増殖症患者にとって大きな負担軽減となる。