New strategy based on the organogenesis signal control for periodontal disease

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390553
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Periodontal dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: IZUMI Yuichi 東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (60159803)
• Co-Investigator(Kenkyū-buntansha): NAGASAWA Toshiyuki 北海道医療大学, 准教授 (90262203) ; KOBAYASHI Hiroaki 東京医科歯科大学, 医歯学総合研究科, 助教 (50396967) ; IWASAKI Kengo 東京医科歯科大学, 医歯学総合研究科, 寄附講座教員 (40401351) ; IWASAKI Kengo 東京医科歯科大学, 医歯学総合研究科, 助教 (50401378)
• Project Period (FY): 2009 – 2011
• Keywords: 歯周免疫機能学

Research Abstract

Wnt5a mRNA expression was up-regulated in chronic periodontitis tissue as compared to healthy control tissue. P. gingivalis LPS induced Wnt5a mRNA in the human monocytic cell line THP-1 with a peak at 4 hrs after stimulation. P. gingivalis LPS induced higher up-regulation of Wnt5a mRNA than E. coli LPS. The LPS receptors TLR2 and TLR4 were equally expressed on the surface of THP-1 cells. P. gingivalis LPS induced IkBa degradation and was able to increase the NF-kB binding activity to DNA. P. gingivalis LPS-induced Wnt5a expression was inhibited by NF-kB inhibitors, suggesting NF-kB involvement. Furthermore, IFN-g synergistically enhanced the P. gingivalis LPS-induced production of Wnt5a. Pharmacological investigation and siRNA experiments showed that STAT1 was important for P. gingivalis LPS-induced Wnt5a expression. These results suggest that the modulation of Wnt5a expression by P. gingivalis may play an important role in the periodontal inflammatory process and serve a target for the development of new therapies.

Research Products

• [Journal Article] Modulation of Wnt5a expression by periodontopathic bactreia (2012)
  • Author(s): Hiromi Nanbara, Nawarat Wara-aswapati, Toshiyuki Nagasawa, Yasuhiro Yoshida, Reiko Yashiro, Yukiko Bando, Hiroaki Kobayashi, Janjura Khongcharoensuk, Doosadee Hormdee, Waranuch Pitiphat, Jason A. Boch, Yuichi Izumi
  • Journal Title: Plos ONE Volume: 7(4) Pages: e34434
• [Journal Article] Current and future periodontal tissue engineering (2011)
  • Author(s): Izumi Yuichi, Aoki Akira, Yamada Yuichi, Kobayashi Hiroaki, Iwata Takanori, Akizuki Tatsuya, Suda Tomonari, Nakamura Sayaka, Wara-Aswapati Nawarat, Ueda Minoru, Ishikawa I
  • Journal Title: Periodontol 2000 Volume: 56(1) Pages: 166-87
• [Journal Article] Comparison of different tissue-derived stem cell sheets for periodontal regeneration in a canine 1-wall defect model (2011)
  • Author(s): Tsumanuma Y, Iwata T, Washio K, Yoshida T, Yamada A, Takagi R, Ohno T, Lin K, Yamato M, Ishikawa I, Okano T, Izumi Y
  • Journal Title: Biomaterials Volume: 32(25) Pages: 5819-25
• [Journal Article] Hydrogen Sulfide Causes Apoptosis in Human Pulp Stem Cells (2011)
  • Author(s): Kobayashi C, Yaegaki K, Calenic B, Ishkitiev N, Imai T, Ii H, Aoyama I, Kobayashi H, Izumi Y, Haapasalo M
  • Journal Title: J Endod Volume: 37 Pages: 479-484
• [Journal Article] Porphyromonas gingivalis promotes murine abdominal aortic aneurysms via matrix metalloproteinase-2 induction (2011)
  • Author(s): Aoyama N, Suzuki J, Wang D, Ogawa M, Kobayashi N, Hanatani T, Takeuchi Y, Izumi Y, Isobe M
  • Journal Title: J Periodontal Res Volume: 46(2) Pages: 176-183
• [Journal Article] Comparison of characteristics of periodontal ligament cells obtained from outgrowth and enzyme-digested culture methods (2011)
  • Author(s): Tanaka K, Iwasaki K, Fegali K, Komaki M, Ishikawa I, Izumi Y
  • Journal Title: Arch Oral Biol Volume: 56 Pages: 380-388
• [Journal Article] Relationship between Periodontitis and Diabetes Importance of a Clinical Study to Prove the Vicious Cycle (2010)
  • Author(s): Nagasawa T, Noda M, Katagri S, Takaichi M, Takahashi Y, Wara-Aswapati N, Kobayashi H, Ohara S, Kawaguchi Y, Tagami T, Furuichi Y, Izumi Y
  • Journal Title: Internal Med Volume: 49(10) Pages: 881-885
• [Journal Article] Periodontitis and cardiovascular diseases (2010)
  • Author(s): Suzuki J, Aoyama N, Ogawa M, Hirata Y, Izumi Y, Nagai R, Isobe M
  • Journal Title: Expert Opin Ther Targets Volume: 14(10) Pages: 1-5
• [Presentation] Wnt5a expression by Porphyromonas gingivalis LPS via NF-κB and STAT1 (2011)
  • Author(s): Nanbara H, Kobayashi H, Izumi Y, et al
  • Organizer: The 10th World Congress on Inflammation
  • Place of Presentation: Paris, France
  • Year and Date: 20110625-29
• [Presentation] ヒト単球系細胞THP-1における歯周病原細菌刺激によるWnt5a遺伝子発現について (2011)
  • Author(s): 南原弘美、小林宏明、和泉雄一
  • Organizer: 第54回日本歯周病学会春季学術大会
  • Place of Presentation: 博多
  • Year and Date: 20110527-28
• [Presentation] Functions of PI3K and MAPK on Wnt5a expression in THP-1 (2010)
  • Author(s): Nanbara H, Kobayashi H, Izumi Y, et al
  • Organizer: 58^<th> Japanese Association for Dental Research
  • Place of Presentation: Kokura, Japan
  • Year and Date: 20101100
• [Presentation] P. gingivalis LPS induce Wnt5a via NF-κB and STAT1 signaling pathway (2010)
  • Author(s): Nanbara H, Kobayashi H, Izumi Y, et al
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸
  • Year and Date: 20100800
• [Presentation] Induction of Wnt5a in THP-1 cells by periodontopathic bacteria (2010)
  • Author(s): Nanbara H, Kobayashi H, Izumi Y, et al
  • Organizer: 88^<th> International and American Association for Dental Research
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 20100700