Establishment of an effective three dimensional culture model for screening of molecular targeted drug for periodontitis

2012 Fiscal Year Final Research Report

• Project/Area Number: 21592637
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Periodontal dentistry
• Research Institution: Ohu University (2010-2012); Nihon University (2009)
• Principal Investigator: OHSHIMA Mitsuhiro 奥羽大学, 薬学部, 教授 (30194145)
• Co-Investigator(Kenkyū-buntansha): YAMAGUCHI Yoko 日本大学, 歯学部, 助手 (00239922)
• Co-Investigator(Renkei-kenkyūsha): ABIKO Yoshimitsu 日本大学, 松戸歯学部, 教授 (70050086) ; KATO Mitsuyasu 筑波大学, 人間総合科学研究科, 教授 (70050086)
• Project Period (FY): 2009 – 2012
• Keywords: 歯周免疫機能学

Research Abstract

“In vitro periodontitis model” using collagen gel three-dimensional culture was established combining primary cultured gingival epithelial cells and gingival fibroblasts. Transcriptome analyses revealed several candidate genes for periodontitis. Furthermore, inhibition of activity of FLT-1, one of the products of candidate genes for periodontitis, using small molecule kinase inhibitor successfully controlled collagen gel degradation, suggested a possibility to use this kinase inhibitor as a molecular-targeted drug for periodontitis.

Research Products

• [Journal Article] 歯周炎薬物治療のパラダイムシフト(総説) (2013)
  • Author(s): 大島光宏、山口洋子
  • Journal Title: 日薬理誌 Volume: 141 Pages: 314-320
  • Peer Reviewed
• [Journal Article] High-frequency low-level diode laser irradiation promotes proliferation and migration of primary cultured human gingival epithelial cells (2013)
  • Author(s): Kenichiro Ejiri, Akira Aoki, Yoko Yamaguchi, Mitsuhiro Ohshima, Yuichi Izumi
  • Journal Title: Lasers Med Sci 2013 Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] An integrated expression profiling reveals target genes of TGF-β and TNF-α possibly mediated by microRNAs in lung cancer cells (2013)
  • Author(s): Akira Saito, Hiroshi I Iizuka, Masafumi Horie, Mitsuhiro Ohshima, Yasuyuki Morishita, Yoshimitsu Abiko, Takahide Nagase
  • Journal Title: PLoS ONE 8 Volume: 8 Pages: e56587
  • DOI: doi:10.1016/j.bbrc.2012.05.104.
  • Peer Reviewed
• [Journal Article] Characterization of human lung cancer-associated fibroblasts in three dimensional in vitro co-culture model (2012)
  • Author(s): Masafumi Horie, Akira Saito, Mitsuhiro Ohshima, Yasuyuki Morishita, Jun Nakajima, Tadashi Kohyama, Takahide Nagase
  • Journal Title: Biochem Biophys Res Commun Volume: 423 Pages: 158-163
  • DOI: doi:10.1371/journal.pone.0056587.
  • Peer Reviewed
• [Journal Article] Insulin-like growth factor-binding protein-2 and -3 in gingival crevicular fluid (2010)
  • Author(s): Takenouchi Y, Ohshima M, Yamaguchi Y, Nishida T, Senda N, Idesawa M, Otsuka K, Ito K
  • Journal Title: J Periodontal Res Volume: 45 Pages: 803-808
  • DOI: doi:10.1111/j.1600-0765.2010.01309.x.
  • Peer Reviewed
• [Journal Article] TGF-b signaling in gingival fibroblast-epithelial interaction (2010)
  • Author(s): M. Ohshima, Y. Yamaguchi, M. Matsumoto, P. Micke, T. Takenouchi, N. Nishida, M. Kato, K. Komiyama, Y. Abiko, K. Ito, K. Otsuka, K. Kappert
  • Journal Title: J Dent Res Volume: 89 Pages: 1315-1321
  • DOI: doi:10.1177/0022034510378423.
  • Peer Reviewed
• [Presentation] Super-pulsed low-level diode Laser stimulates cultured human gingival epithelial cells (2013)
  • Author(s): Kenichiro Ejiri, Akira Aoki, Yoko Yamaguchi,Mitsuhiro Ohshima, Yuichi Izumi
  • Organizer: 91^<st>IADR
  • Place of Presentation: Seattle, USA
  • Year and Date: 20130300
• [Presentation] 低出力半導体レーザー照射が初代培養ヒト歯肉上皮細胞に及ぼす効果 (2012)
  • Author(s): 江尻健一郎、青木 章、山口洋子、大島光宏、和泉雄一
  • Organizer: 第24回日本レーザー歯学会総会・学術大会
  • Place of Presentation: 神戸
  • Year and Date: 20121200
• [Presentation] FLT-1は歯周炎治療の標的分子となり得るか (2012)
  • Author(s): 大島光宏、山口洋子、安孫子宜光
  • Organizer: 第54回歯科基礎医学会学術大会・総会
  • Place of Presentation: 郡山
  • Year and Date: 20120900
• [Presentation] (2012)
  • Author(s): 大島光宏、山口洋子、張 月琳、佐久間淳
  • Organizer: 2012年度日本機会学会年次大会
  • Place of Presentation: 金沢
  • Year and Date: 20120900
• [Presentation] 低出力半導体レーザー照射が培養ヒト歯肉上皮細胞に及ぼす効果 (2012)
  • Author(s): 江尻健一郎、青木 章、山口洋子、大島光宏、和泉雄一
  • Organizer: 第136回日本歯科保存学会春季学術大会
  • Place of Presentation: 沖縄
  • Year and Date: 20120600
• [Presentation] 受容体チロシンキナーゼ阻害剤による非外科的顎〓胞治療法の開発 (2011)
  • Author(s): 大島光宏、山口洋子、石井輝彦、大木秀郎
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 20110900
• [Presentation] FLT-1 represents a potential therapeutic target in human periodontitis (2011)
  • Author(s): Mitsuhiro Ohshima, Yoko Yamaguchi, Yoshimitsu Abiko
  • Organizer: GRC in Periodontal Diseases
  • Place of Presentation: Davidson College, Davidson, NC, USA
  • Year and Date: 20110700
• [Presentation] 生体外歯周炎モデルによる生薬のスクリーニン グ (2010)
  • Author(s): 山口洋子、鳥居塚和生、大島光宏
  • Organizer: 第33回日本分子生物学会年会、第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 20101200
• [Presentation] 生薬による生体外歯周炎モデルのコラーゲン分解阻害 (2010)
  • Author(s): 山口洋子、鳥居塚和生、大島光宏
  • Organizer: 第49回日本薬学会東北支部大会
  • Place of Presentation: 郡山
  • Year and Date: 20101000
• [Presentation] 三次元培養法を用いた新規歯周炎治療薬のスクリーニング (2010)
  • Author(s): 山口洋子、大島光宏
  • Organizer: 第42回日本結合組織学会・第57回マトリックス研究会合同学術集会
  • Place of Presentation: 秋田
  • Year and Date: 20100800
• [Presentation] A novel drug screening system for periodontitis using 3D culture (2010)
  • Author(s): Ohshima M, Yamaguchi Y, Abiko Y
  • Organizer: GRC in Periodontal Diseases
  • Place of Presentation: Colby-Sawyer College, New London, NH, USA
  • Year and Date: 20100800
• [Remarks]
  • URL: http://www.ohu-u.ac.jp/newinfo/2010/20100924.html
• [Patent(Industrial Property Rights)] 歯周炎治療薬 (2012)
  • Inventor(s): 山口洋子、大島光宏
  • Industrial Property Rights Holder: 日本大学
  • Industrial Property Number: 特願2012-086327
  • Filing Date: 2012-04-05
• [Patent(Industrial Property Rights)] 口腔癌細胞浸潤阻害剤 (2011)
  • Inventor(s): 山口洋子、大島光宏、鳥居塚和生
  • Industrial Property Rights Holder: 日本大学、昭和大学
  • Industrial Property Number: 特願2011-220423
  • Filing Date: 2011-10-04
• [Patent(Industrial Property Rights)] 顎嚢胞治療剤 (2010)
  • Inventor(s): 山口洋子、大島光宏
  • Industrial Property Rights Holder: 日本大学
  • Industrial Property Number: 特願2010-152872
  • Filing Date: 2010-07-05
• [Patent(Industrial Property Rights)] コラーゲン分解阻害剤 (2010)
  • Inventor(s): 大島光宏、山口洋子、鳥居塚和生
  • Industrial Property Rights Holder: 日本大学、昭和大学
  • Industrial Property Number: 特願2010-132206
  • Filing Date: 2010-06-09
• [Patent(Industrial Property Rights)] 歯周炎治療薬 (2010)
  • Inventor(s): 大島光宏、山口洋子
  • Industrial Property Rights Holder: 日本大学
  • Industrial Property Number: 特願2010-024339
  • Filing Date: 2010-02-05
• [Patent(Industrial Property Rights)] 歯肉上皮細胞の培養方法 (2009)
  • Inventor(s): 山口洋子、大島光宏
  • Industrial Property Rights Holder: 日本大学
  • Industrial Property Number: 特願2009-231339
  • Filing Date: 2009-10-05
• [Patent(Industrial Property Rights)] 生体外創傷治癒試験用用具または創傷作製方法 (2009)
  • Inventor(s): 山口洋子、大島光宏
  • Industrial Property Rights Holder: 日本大学
  • Industrial Property Number: 特願2009-212903
  • Filing Date: 2009-09-15