Research on developmental mechanisms of drug-induced gingival overgrowth: experiments in animal and cellular levels

• Project/Area Number: 13672144
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 矯正・小児・社会系歯学
• Research Institution: Osaka University
• Principal Investigator: MORISAKI Ichijiro Osaka University Dental Hospital Professor, 歯学部附属病院, 教授 (30116115)
• Co-Investigator(Kenkyū-buntansha): AKIYAMA Shigehisa Osaka University Dental Hospital Associate Professor, 歯学部附属病院, 助教授 (00283797)
• Project Period (FY): 2001 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥2,900,000 (Direct Cost: ¥2,900,000); Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: phenytoin / cyclosporin / nifedipine / fibroblast / apotosis / ketoconazole / ニクエジピン

Research Abstract

1. Human Gingival Fibroblast Experiments: in vitro
1) When effects ofnifedipine, a calcium channel btocfcer, on cell proliferation and apoptosis were examined in human gingival fibroblast (HGF) cultures, both of these were suppressed by the drug in a dose dependent manner
2) Nifedipine inhibited lipopolysaccharide (LPS)induced nitric oxide (NO) production and apoptosis of macrophage like cells (RAW264). Furthermore, LPSinduced NO synthetase (iNOS) production was also inhibited by adding nifedipine to the RAW 264 ceil cultures
3) LPS stimulation induced the apoptosis ofHGF cultured with RAW264, however, this apoptosis was suppressed by the addition of nifedipine to the culture
4) Phenytoin enhanced the mRNA production of matrix metaloproreases (MMPs) and their inhibitors in the HGF cultures
These findings are suggesting that the close relationship exists between the effects ofnifedipine or phenytoin on the proliferation, apoptosis and inflammatory reaction of HGF and the druginduced gingival overgrowth
2. Drug Interaction in Gingival Overgrowth in Rats
1) To elucidate the effects of drug interaction on gingival overgrowth, rats were treated with nifedipine and/or ketoconazole which affects the nifedipine metabolism. Ketoconazole treatment induced higher blood nifedipine level and more severe gingival overgrowth in rats than those treated with nifedipine only
2) When rats were treated with nifedipine and administered grapefruitjuice or bergamot oil concomitantly, an increase in severity of nifedipineinduced gingival overgrowth was found in rats given

Research Products

• [Publications] 森崎市治郎: "薬物誘発性歯肉肥大の発症要因解析"大阪大学歯学雑誌. 46・2. 55-61 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Fukui, N. et al.: "Gingival Overgrowth in Rats Orally Treated with Large Dose of Phenytoin"Dentistry in Japan. 38. 150-154 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nakagawam I, et al.: "Identification of a new variant of fimA gene of Porphyromonas gingivalis and its distribution in adutls and disabled population with periodontitis"Journal of Periodontal Research. 37. 425-432 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kimura, S. et al.: "Periodontopathic Bacterial Infection in Childhood"Journal of Periodontology. 73. 20-26 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 森崎市治郎: "イラストレイテッド・クリニカルデンティストリー4.小児歯科疾患・口腔病変・不正咬合 障害児の歯科治療"医歯薬出版(株). 250(82-85) (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ichijiro,MORISAKI: "Analyses for pathogenetic factors of drug-induced gingival overgrowth: A review"Journal ofOsaka University Dental Society. 46(2) in Japanes. 55-61 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hatsuko,FUKUI, Takahiro,KATO, Mikiko,HAYASHI, Jumpei,MLTRAKAMI, Keiko,KONISHl, Katsura,UEDA, Shigehisa,AKIYAMA, Atsuo,AMANO, Ichijiro,MORISAKI: "Gingival overgrowth in rats orally treated with large dose of phenytoin"Dentistry in.Japan. 38. 150-154 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ichiro,NAKAGAWA, Atsuo,AMANO, Ohara,NHMOTO, Ichijiro,MORISAKI, Shigenobu,KllMURA, Shigetada,KAWABATA, Shigeyuki,HAMADA: "Identification of a new variant of fim A gene of Porphyramonas gingivalis and its distribution in adults and disabled population with periodontitis"Journal of Periodontal Research. 37. 425-432 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Shigenpbu,KIMURA, Takashi,OOSHIMA, Miyako,TAKIGLTCHI, Atsuo,AMANO, Ichijiro,MORISAKI, Shigeyuki,HANtADFA: "Periodontopathic bacterial infection in the childhood"Journal of Periodontology. 73. 20-26 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Icihijiro,MORJSAKI: "Dental treatment for children with disabilities."Illustrated Clinical Dentistry 4. Dentistry for the child: oral diseases/malociulusion. Ishiyaku Shuppan Co. Ltd. Tokyo (in Japanese). 82-85 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 森崎市治郎: "薬物誘発性歯肉肥大の発生要因解析"大阪大学歯学雑誌. 46・2. 55-61 (2002)
• [Publications] Fukui, N., et al.: "Gingival Overgrowth in Rats Orally Treated with Large Dose of Phenytoin"Dentistry in Japan. 38. 150-154 (2002)
• [Publications] Nakagawa, I., et al.: "Identification of a New Variant of fimA Gene of Porphyoomonas gingivalis and Its Distribution in Adutls and Disabled Population with Periodontitis"Journal of Periodontal Research. 37. 425-432 (2002)
• [Publications] Kimura, S., et al.: "Periodontopathic Bacterial Infection in Childhood"Journal of Periodontology. 73. 20-26 (2002)
• [Publications] 森崎市治郎: "イラストレイテッド・クリニカルデンティストリー4.小児歯科疾患・口腔病変・不正咬合障害児の歯科治療"医歯薬出版株式会社. 82-85(250) (2002)
• [Publications] Fujimori, Yasushi, et al.: "Inhibition by nifedipine of adherence-and activated macrophage-induced cell death of human gingival fibroblasts"European Journal of Pharmacology. 415. 95-103 (2001)
• [Publications] Morisaki, Ichijiro et al.: "Amlodipine-inducedugingival overgrowth : periodontal responses to stopping and restarting the drug"Special are in Dentistry. 21. 60-62 (2001)
• [Publications] Amano, Atsuo et al.: "Relationship of periodontopathic bacteria with early-onset periodontitis in Down's syndrome :"Journal of Periodontology. 72. 368-373 (2001)
• [Publications] 秋山茂久, 他: "知的障害者における薬物誘発性歯肉肥大に対するEriYAGレーザーの応用"日本歯科評論. 61. 109-111 (2001)
• [Publications] Kimura, S. et al.: "Periodontopathic bacterial infection in Childhood"Journal of Periodontology. 73. 20-26 (2002)
• [Publications] Nakagawa, Ichiro et al.: "Identification of a new variant of fim A gone of Porphvromonas gingivalis and its distribution in adults and disabled population with periodontitis"Journal of Periodontal Research. (in press).