Elucidation and reguration of the periodontal disease progression mechanism based on new inflammation adjustments(ANA and HMGB-1)

2008 Fiscal Year Final Research Report

• Project/Area Number: 18390561
• 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 (2007-2008); Kagoshima University (2006)
• Principal Investigator: IZUMI Yuichi Tokyo Medical and Dental University, 大学院・医歯学総合研究科, 教授 (60159803)
• Co-Investigator(Kenkyū-buntansha): MARUYAMA Ikuro 鹿児島大学, 医歯(薬)学総合研究科, 教授 (20082282) ; MACHIGASHIRA Miho 鹿児島大学, 医学部・歯学部附属病院, 講師 (80253897) ; NAKAMURA Toshiaki 鹿児島大学, 医歯(薬)学総合研究科, 助教 (60381183) ; KOBAYASHI Hiroaki 東京医科歯科大学, 大学院・医歯学総合研科, 助教 (50396967)
• Project Period (FY): 2006 – 2008
• Keywords: 歯周病 / HMGB-1 / アナンダマイド / 炎症

Research Abstract

歯周炎の疾患進行における、新規炎症メディエーターであるアナンダマイド(ANA)とHigh Mobility Group Box-1(HMGB-1)に関する研究を行った。ANAは神経性物質であり、神経末端から放出される。このANAは歯周炎局所で発現が亢進しており、歯周炎疾患進行において神経機構が関与している可能性が示唆された。HMGB-1は核内では転写因子として働き、細胞外では起炎性物質として働く。HMGB-1の歯周組織での発現が認められ、疾患進行に関与している可能性が示唆された。

Research Products

• [Journal Article] Cyclooxygenase-2-derived prostaglandin E2 is involved in vascular endothelial growth factor production in interleukin-1α-stimulated human periodontal ligament cells (2009)
  • Author(s): Bando Y, Noguchi K, Kobayashi H, Yoshida N, Ishikawa I, Izumi Y
  • Journal Title: J Periodont Res 44(3) Pages: 395-401
• [Journal Article] Periodontal status and Prevotella intermedia antibody in acute coronary syndrome (2008)
  • Author(s): Soejima H., Oe Y.,Nakayama, H., Matsuo K., Fukunaga T., Sugamura K., Kawano H., Sugiyama S., Shinohara M., Izumi Y., Ogawa H.
  • Journal Title: Int J Cardiol, 2008,doi 10, 1016(/j.ijcard) Pages: 057
• [Journal Article] The role of water channel aquaporin 3 in the mechanism of TNF-alpha-mediated proinflammatory events : Implication in periodontal inflammation (2008)
  • Author(s): S. Tancharoen, T. Matsuyama, K. Abeyama, K. Matsushita, K. Kawahara, V. Sangalungkarn, M. Tokuda, T. Hashiguchi, I. Maruyama, Y. Izumi
  • Journal Title: J Cell Physiol 217 Pages: 338-349
• [Journal Article] IL-6 induces osteoblastic differentiation of periodontal ligament cells (2008)
  • Author(s): K. Iwasaki, M. Komaki, K. Mimori, E. Leon, Y. Izumi, I. Ishikawa
  • Journal Title: J Dent Res 87 Pages: 937-942
• [Journal Article] Changes in serum interleukin-6, C-reactive protein and thrombomodulin levels under periodontal ultrasonic debridement (2008)
  • Author(s): Y. Ushida, G. Koshy, Y. Kawashima, M. Kiji, M. Umeda, H. Nitta, T. Nagasawa, I. Ishikawa, Y. Izumi
  • Journal Title: J Clin Periodontol 35 Pages: 969-975
• [Journal Article] Molecular mimicry of Aggregatibacter actinomycetemcomitans with b2 glycoprotein I (2008)
  • Author(s): D. Wang, T. Nagasawa, Y. Chen, Y. Ushida, H. Kobayashi, Y. Takeuchi, M. Umeda, Y. Izumi
  • Journal Title: Oral Microbiol Immunol 23 Pages: 401-405
• [Journal Article] Injectable growth/differentiation factor-5/recombinant human collagen composite induces endochondral ossification via sox9 expression and angiogenesis in murine calvariae (2008)
  • Author(s): Kadomatsu, H., Matsuyama, T., Yoshimoto, T., Negishi, Y., Sekiya, H., Yamamoto, M. Izumi, Y.,
  • Journal Title: J. Periodontal Res 43 Pages: 483-489
• [Journal Article] Significance of thrombomodulin release from gingival epithelial cells in periodontitis patients (2008)
  • Author(s): Matsuyama, T., Tokuda, M., Izumi, Y.
  • Journal Title: J Periodontal Res 43 Pages: 379-385
• [Journal Article] Tumor necrosisi factor-alpha stimulates gingival epithelial cells to release high mobility-group box 1 (2008)
  • Author(s): Morimoto, Y., Kawahara, K-I., Tancharoen, S., Kikuchi, K., Matsuyama, T., Hashiguchi, T., Izumi, Y., Maruyama, I.
  • Journal Title: J Periodontal Res. 43 Pages: 76-83
• [Journal Article] Periodontitis may increase the risk of peripheral arterial disease (2008)
  • Author(s): Yi-Wen Chen, Makoto Umeda, Toshiuki Nagasawa, Yasuo Takeuchi, Yi Huang, Yoshinori Inoue, Takehisa Iwai, Yuichi Izumi, Isao Ishikawa
  • Journal Title: European Journal of Vascular and Endovascular Surgery 35 Pages: 153-158
• [Journal Article] Comparison of injectable calcium phosphate bone cement grafting and open flap debridement in periodontal intrabony defects A randomized clinical trial (2008)
  • Author(s): Shirakata, Y., Setoguchi, T., Machigashira, M., Matsuyama, T., Furuichi, Y., Hasegawa, K., Nakamura, T. and Izumi, Y.
  • Journal Title: J. Periodontol. 79 Pages: 25-32
• [Journal Article] Surface properties and biocompatibility of acid-etched titanium (2008)
  • Author(s): Iwaya Y, Machigashira M, Kanbara K, Miyamoto M, Noguchi K, Izumi Y, Ban S
  • Journal Title: Dent Mater J 27 Pages: 415-421
• [Journal Article] Effect of rhBMP-2 with PLGA/gelatin sponge type(PGS)carrier on alveolar ridge augmentation in dogs (2008)
  • Author(s): Kawakatsu N, Oda S, Kinoshita A, Kikuchi S, Tsuchioka H, Akizuki T,Hayashi C, Kokubo S, Ishikawa I, Izumi Y.
  • Journal Title: Journal of Oral Rehabilitation 35 Pages: 647-655
• [Journal Article] The effect of chemical and/or mechanical conditioning on the Er : YAG laser treated root cementum : analysis of surface morphology and periodontal ligament fibroblast attachment (2008)
  • Author(s): Maruyama H, Aoki A, Sasaki KM, Takasaki AA, Iwasaki K, Ichinose S, Oda S, Ishikawa I, Izumi Y.
  • Journal Title: Lasers Surg Med 40(3) Pages: 211-222
• [Journal Article] Hydrogen sulfide inhibits cell proliferation and induces cell cycle arrest via an elevated p21Cip1 level in Ca9-22 cells (2008)
  • Author(s): Takeuchi H, Setoguchi T, Machigashira M, Kanbara K, Izumi Y.
  • Journal Title: J Periodontal Res 43 Pages: 90-95
• [Journal Article] Human gingival fibroblasts release HMGB1through active and passive pathways (2007)
  • Author(s): Feghali K, Iwasaki K, Tanaka K, Komaki M, Machigashira M, Ishikawa I, Izumi Y
  • Journal Title: Oral Microbiol Immunol 24 Pages: 1-7
• [Journal Article] High incidence of actinobacillus actinomycetemcomitans infection in acute coronary syndrome (2007)
  • Author(s): Sakurai K, Wang D, Suzuki J, Umeda M, Nagasawa T, Izumi Y, Ishikawa I, Isobe M.
  • Journal Title: Int Heart J 48 Pages: 663-675
• [Journal Article] Establishment of cell lines that exhibit pluripotency from miniature swine periodontal ligaments (2007)
  • Author(s): M. Ibi, A. Ishisaki, M. Yamamoto, A. Wada, T. Kozakai, A. Nakashima, J. Iida, S. Takao, Y. Izumi, A. Yokoyama, M. Tamura,
  • Journal Title: Arch Oral Biol 52 Pages: 1002-1008
• [Journal Article] Functional polymorphisms of the FPR1 gene and aggressive periodontitis in Japanese (2007)
  • Author(s): Gunji, T., Onouchi, Y., Nagasawa, T., Katagiri, S., Watanabe, H., Kobayashi, H., Arakawa, S., Noguchi, K., Hata, A., Izumi, Y., Ishikawa, I.
  • Journal Title: Biophys. Res. Commun 364 Pages: 7-13
• [Journal Article] Favorable periodontal healing of 1-wall infrabony defects after application of calcium phosphate cement wall alone or in combination with enamel matrix derivative : A pilot study with canine mandibles (2007)
  • Author(s): Shirakata, Y., Yoshimoto, T., Goto, H., Yonamine, Y., Kadomatsu, H., Miyamoto, M., Nakamura, T., Hayashi, C. and Izumi, Y.
  • Journal Title: J. Periodontol 78 Pages: 889-898
• [Journal Article] Platelet-rich plasma/osteoblasts complex induces bone formation via osteoblastic differentiation following subcutaneous transplantation (2006)
  • Author(s): H. Goto, T. Matsuyama, M. Miyamoto, Y. Yonamine, Y. Izumi
  • Journal Title: J Periodont Res 41 Pages: 455-462
• [Journal Article] B and T Lymphocytes Are the Primary Sources of RANKL in the Bone Resorptive Lesion of Periodontal Disease (2006)
  • Author(s): Toshihisa Kawai, Takashi Matsuyama, Yoshitaka Hosokawa, Seicho Makihira, Makoto Seki, Nadeem Y. Karimbux, Reginaldo B. Goncalves, Paloma Valverde, Serge Dibart, Yi-Ping Li, Leticia A. Miranda, Cory W.O. Ernst, Yuichi Izumi, Martin A. Taubman
  • Journal Title: Am J Pathol 169 Pages: 987-998
• [Journal Article] Gene Transfer to Corneal Epithelium and Keratocytes Mediated by Ultrasound with Microbubbles (2006)
  • Author(s): Shozo Sonoda, Katsuro Tachibana, Eisuke Uchino, Akiko Okubo, Matsuo Yamamoto, Kenji Sakoda, Toshio Hisatomi, Koh-Hei Sonoda, Yoichi Negishi, Yuichi Izumi, Sonshin Takao, Taiji Sakamoto
  • Journal Title: Invest Ophthalmol Vis Sci 47 Pages: 558-564
• [Journal Article] Endocannabinoid, anandamide in gingival tissue regulates the periodontal inflammation through NF-kB pathway inhibition (2006)
  • Author(s): Yumiko Nakajima, Yasushi Furuichi, Kamal Krishna Biswas, Teruto Hashiguchi, Ko-ichi Kawahara, Kazuyo Yamaji, Tomonori Uchimura, Yuichi Izumi, Ikuro Maruyama
  • Journal Title: FEBS Letters 580 Pages: 613-619
• [Journal Article] Simvastatin Decreases IL-6 and IL-8 Production in Epithelial Cells (2006)
  • Author(s): K. Sakoda, M. Yamamoto, Y. Negishi, J.K. Liao, K. Node, Y. Izumi
  • Journal Title: J Dent Res 85 Pages: 520-523
• [Journal Article] Recombinant human growth/differentiation factor-5 induced bone formation on murine calvariae (2006)
  • Author(s): T. Yoshimoto, M. Yamamoto, H. Kadomatsu, K. Sakoda, Y. Yonamine, Y. Izumi
  • Journal Title: J Periodont Res 41 Pages: 140-147
• [Journal Article] Early cellular responses of osteoblast-like cells on acid- etching and alkaline treated titanium (2006)
  • Author(s): M. Miyamoto, H. Kono, A. Yuda, H. Goto, M. Machigashira, S. Ban, Y. Izumi
  • Journal Title: Key Engineering Materials 309-311 Pages: 403-406
• [Journal Article] Arginine-specific gingipains from Porphyromonas gingivalis deprive protective functions of secretory leukocyte protease inhibitor in periodontal tissue (2006)
  • Author(s): T. Into, M. Inomata, Y. Kanno, T.Matsuyama, M.Machigashira, Y.Izumi, T. Imamura, M. Nakashima, T. Noguchi and K. Matsushita
  • Journal Title: Clin Exp Immunol 145(3) Pages: 545-554
• [Journal Article] Periodontal tissue regeneration using fibroblast growth factor-2
  • Author(s): Kitamura M., Nakashima K., Kowashi Y., Fujii T., Shimauchi H., Sasano T., Furuuchi T., Fukuda M., Noguchi T., Shibutani T., Iwayama Y., Takashiba S., Kurihara H., Ninomiya M., Kido J., Nagata T., Hamachi T., Maeda K., Hara Y., Izumi Y., Hirofuji T., Imai E., Omae M., Watanuki M., Murakami S.
  • Journal Title: Randomized controlled phase II clinical trial PLos ONE 3(7) Pages: e2611(Doi10.1371/j.pone.0002611)
• [Presentation] 軟骨細胞においてBMP2の誘導するRANKL活性化はRANKL promoterのRunx2 binding sitesを介する (2009)
  • Author(s): 臼井通彦
  • Organizer: 第50回春季日本歯周病学会
  • Place of Presentation: 横須賀
  • Year and Date: 2009-05-19
• [Presentation] Human gingival fibroblasts release HMGB1 through active and passive pathways (2008)
  • Author(s): Feghali K
  • Organizer: 56^<th> Annual meeting of Japanese Association of Dental Research
  • Place of Presentation: Nagoya
  • Year and Date: 20081129-30
• [Presentation] RANKL expression in abdominal aortic aneurysms might be associated with periodontopathic bacteria (2008)
  • Author(s): Suda T
  • Organizer: 94^<th> Annual Meetimg of the American Academy of Periodontology
  • Place of Presentation: Seattle
  • Year and Date: 20081106-09
• [Presentation] 歯周炎患者由来の歯肉溝滲出液中に存在するForsythia detaching factor : FDFに対する抗体価と歯周炎の病態との関連性の解析 (2008)
  • Author(s): 大西英知
  • Organizer: 第50回歯科基礎医学学術大会
  • Place of Presentation: 東京
  • Year and Date: 20080923-26
• [Presentation] Gingival Epithelial Cells Potently Release HMGB1 : Implication in Periodontitis (2008)
  • Author(s): Morimoto Y
  • Organizer: The 86^<th> General session of international association of dental Research
  • Place of Presentation: Toronto
  • Year and Date: 20080702-05
• [Presentation] Human gingival fibroblasts release HMGB1 after stimulation with LPS (2008)
  • Author(s): Feghali K
  • Organizer: The 86^<th> General session of international association of dental Research
  • Place of Presentation: Toronto
  • Year and Date: 20080702-05
• [Presentation] 歯周創傷治癒に内因性カンナビノイドが関与している (2008)
  • Author(s): 小薗清香
  • Organizer: 第51回春季日本歯周病学会学術大会
  • Place of Presentation: 大宮
  • Year and Date: 20080425-26
• [Presentation] β-2 glycoprotein Iと相同性を有する歯周病原細菌由来ペプチドに対する歯周炎患者の抗体反応 (2008)
  • Author(s): 長澤敏行
  • Organizer: 第51回春季日本歯周病学会学術大会
  • Place of Presentation: 大宮
  • Year and Date: 20080425-26
• [Presentation] High Mobility Group Box 1(HMGB1)がヒト歯根膜に与える影響 (2008)
  • Author(s): 長谷川奈美
  • Organizer: 第51回春季日本歯周病学会学術大会
  • Place of Presentation: 大宮
  • Year and Date: 20080425-26
• [Presentation] 腹部大動脈瘤でのRANKL発現と歯周病原細菌の検出との関連 (2008)
  • Author(s): 須田智也
  • Organizer: 口腔病学会第73回学術大会
  • Place of Presentation: 東京
  • Year and Date: 2008-12-16
• [Presentation] 歯周炎患者と健常者における歯肉溝滲出液中の抗FDF抗体価の比較 (2008)
  • Author(s): 大西英知
  • Organizer: 第51回秋季日本歯周病学会学術大会
  • Place of Presentation: 四日市
  • Year and Date: 2008-10-19
• [Presentation] 超音波スケーラーによる full-mouth debridement後の血清IL-6, CRPおよび可溶性トロンボモジュリンの変動 (2008)
  • Author(s): 牛田由佳
  • Organizer: 第51回秋季日本歯周病学会学術大会
  • Place of Presentation: 四日市
  • Year and Date: 2008-10-19
• [Presentation] High Mobility Group Box 1は歯根膜細胞のIL-8産生を増強する (2008)
  • Author(s): 長谷川奈美
  • Organizer: 第29回日本炎症・再生医学会
  • Place of Presentation: 都市センターホテル
  • Year and Date: 2008-07-09
• [Presentation] Molecular mimicry of Actinobacillus actinomycetemcomitans with beta-2 glycoprotein I (2007)
  • Author(s): Nagasawa T
  • Organizer: American Academy of Periodontology 93^<rd> Annualmeeting
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20071027-30
• [Presentation] IL-23 production from monocytes stimulated with periodontopathic bacteria (2007)
  • Author(s): Kobayashi H
  • Organizer: American Academy of Periodontology 93^<rd> Annual Meeting
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20071027-30
• [Presentation] AP-1 suppresses osteoprotegerin synthesis in periodontal ligament fibroblasts (2007)
  • Author(s): Suda T
  • Organizer: American Academy of Periodontology 93^<rd> Annual Meeting
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20071027-30
• [Presentation] Effect of PGE_2 on VEGF production in human periodontal ligament cells (2007)
  • Author(s): Bando Y
  • Organizer: The 7^<th> Asian Pacific Society of Periodontology Meeting(APSP 2007)
  • Place of Presentation: Beijing, China
  • Year and Date: 20070921-22
• [Presentation] Actinobacillus actinomycetemcomitans infection and acute coronary syndrome (2007)
  • Author(s): Wang D
  • Organizer: The 7th Asian Pacific Society of Periodontology Meeting(APSP 2007)
  • Place of Presentation: Beijing, China
  • Year and Date: 20070921-22
• [Presentation] ヒト歯肉上皮細胞のIL-8産生に及ぼすHigh Mobility Group Box 1(HMGB1)の影響 (2007)
  • Author(s): 森元陽子
  • Organizer: 第50回秋季日本歯周病学会50周年記念大会
  • Place of Presentation: 東京
  • Year and Date: 20070921-22
• [Presentation] 歯周病がBurger病患者における抗Cardiolipin抗体に与える影響 (2007)
  • Author(s): 陳イ紋
  • Organizer: 第50回秋季日本歯周病学会50周年記念大会
  • Place of Presentation: 東京
  • Year and Date: 20070921-22
• [Presentation] 歯根膜細胞における転写因子AP-1によるOPG抑制効果について (2007)
  • Author(s): 須田智也
  • Organizer: 第50回秋季日本歯周病学会50周年記念大会
  • Place of Presentation: 東京
  • Year and Date: 20070921-22
• [Presentation] アナンダマイドによる歯周病の炎症制御 (2007)
  • Author(s): 中島結実子
  • Organizer: 第50回春季日本歯周病学会学術大会
  • Place of Presentation: 神奈川
  • Year and Date: 20070518-19
• [Presentation] Production of BMP-2 by Human periodontal fibroblasts stimulated with TGF-β (2007)
  • Author(s): Yashiro R
  • Organizer: Tissue Engineering International & Regenerative Medicine Society Asia-Pacific Chapter Meeting
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2007-12-05
• [Presentation] 慢性歯周炎患者の歯周病原性細菌に対する血清抗体価に与える喫煙の影響 (2007)
  • Author(s): 甘美和
  • Organizer: 第50回春季日本歯周病学会
  • Place of Presentation: 横須賀
  • Year and Date: 2007-05-19
• [Presentation] The Effectiveness of TACE Inhibitor : New Option for Treating Periodontal Inflammation (2006)
  • Author(s): M. Machigashira
  • Organizer: Europerio5
  • Place of Presentation: IFEMA Madrid, Spain
  • Year and Date: 20060629-0701
• [Presentation] Expression of High Mobility Group Box 1(HMGB1)in gingival epithelial cells (2006)
  • Author(s): Y. Morimoto
  • Organizer: Europerio 5
  • Place of Presentation: IFEMA Madrid, Spain
  • Year and Date: 20060629-0701
• [Presentation] Endocannabinoid, anandamide in gingival tissue regulates the periodontal inflammation through NF-κB pathway inhibition (2006)
  • Author(s): Y. Nakajima
  • Organizer: Europerio 5
  • Place of Presentation: IFEMA Madrid, Spain
  • Year and Date: 20060629-0701