Development of molecular targeted drug for periodontitis based on the causative genes.

• Project/Area Number: 15K15768
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Periodontology
• Research Institution: Ohu University
• Principal Investigator: Mitsuhiro Ohshima 奥羽大学, 薬学部, 教授 (30194145)
• Co-Investigator(Kenkyū-buntansha): 山口 洋子 日本大学, 歯学部, 助教 (00239922)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 歯周炎 / 生体外歯周炎モデル / HGF / miRNA / FLT1 / 線維芽細胞

Outline of Final Research Achievements

We have made a list of candidate genes for periodontitis using gene expression profiling data of in vitro periodontitis model which includes periodontitis causative fibroblasts. Inhibiting candidate genes products, collagen degradation was significantly decreased. It will make possible to molecular targeted therapy for periodontitis for the first time. We also demonstrated that periodontitis-causative fibroblasts are clearly different from normal gingival fibroblasts supported by RIKEN FANTOM5 Project, and established a detection method by PCR.

Research Products

• [Int'l Joint Research] Uppsala University(Sweden)
• [Int'l Joint Research] Charite(Germany)
• [Int'l Joint Research] Harry Perkins Institute(オーストラリア)
• [Int'l Joint Research] ウプサラ大学(スウェーデン)
• [Int'l Joint Research] フンボルト大学(ドイツ)
• [Int'l Joint Research] フォーサイス研究所(米国)
• [Journal Article] MicroRNA profiling in gingival crevicular fluid of periodontitis: a pilot study (2017)
  • Author(s): Akira Saito, Masafumi Horie, Kenichiro Ejiri, Akira Aoki, Sayaka Katagiri, Shogo Maekawa, Shinta Suzuki, Sophannary Kong, Tsuneto Yamauchi, Yoko Yamaguchi, Yuichi Izumi, Mitsuhiro Ohshima
  • Journal Title: FEBS Open Bio Volume: 印刷中
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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.
  • Journal Title: Sci Rep Volume: 6 Issue: 1
  • DOI: 10.1038/srep33666
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Fibroblast VEGF-receptor 1 expression as molecular target in periodontitis (2016)
  • Author(s): Ohshima M, Yamaguchi Y, Ambe K, Horie M, Saito A, Nagase T, Nakashima K, Ohki H, Kawai T, Abiko Y, Micke P, Kappert K
  • Journal Title: J Clin Periodontol Volume: 43(2) Issue: 2 Pages: 128-37
  • DOI: 10.1111/jcpe.12495
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 歯肉溝滲出液miRNA による新しい歯周炎診断法 (2016)
  • Author(s): 齋藤 朗, 堀江真史, 江尻健一郎, 青木章, 鈴木伸太, 前川省吾, 片桐さやか, Sophannary Kong, 山内恒人, 山口洋子, 和泉雄一, 大島光宏
  • Organizer: 東北地区歯科医学会
  • Place of Presentation: 宮城県歯科医師会館（宮城県仙台市）
  • Year and Date: 2016-11-05
• [Presentation] CAGE revealed novel biomarker of periodontitis-associated fibroblasts (2015)
  • Author(s): Masafumi Horie, Yoko Yamaguchi, Akira Saito, Takahide Nagase, Masayoshi Itoh , Hideya Kawaji, Timo Lassmann, Piero Carninci, Yoshihide Hayashizaki, Alistair Forrest, The FANTOM consortium, Marina Lizio, Masahiro Kondo, Tatsuo Suzutani, Patrick Micke, and Mitsuhiro Ohshima
  • Organizer: IMGC2015
  • Place of Presentation: 横浜市
  • Year and Date: 2015-11-08
  • Int'l Joint Research
• [Patent(Industrial Property Rights)] 歯周炎治療薬及び歯周炎治療用組成物 (2016)
  • Inventor(s): 大島光宏、山口洋子
  • Industrial Property Rights Holder: 日本大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-146593
  • Filing Date: 2016-07-26