Development of new therapy for periodontal disease based on regulating exocytosis

• Project/Area Number: 19390538
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Periodontal dentistry
• Research Institution: National Institute for Longevity Sciences,NCGG ; 国立長寿医療センター研究所
• Principal Investigator: MATSUSHITA Kenji 国立長寿医療センター研究所, 口腔疾患研究部, 部長 (90253898)
• Co-Investigator(Kenkyū-buntansha): INTO Takeshi 国立長寿医療センター研究所, 口腔疾患研究部, 室長 (10360918)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2008: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000); Fiscal Year 2007: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
• Keywords: 免疫・感染・炎症 / サイトカイン / 高血圧 / 歯周病 / 開口放出 / 炎症性サイトカイン / 歯周免疾機能学 / 膜輸送 / 医薬分子設計 / 細胞情報伝達機構

Research Abstract

We explored meaning of exocytosis on pathogenesis of periodontal disease and possibility of that regulation. We found that various stimulants from periodontopathic bacteria induced exocytosis in keratinocytes, immune cells, and endothelial cells in periodontal tissue and it was regulated nitric oxide.

Research Products

• [Journal Article] Attenuation of LPS-induced iNOS expression by 1, 5-anhydro-D-fructose (2009)
  • Author(s): Meng X, Kawahara KI, Matsushita K, Nawa Y, Shrestha B, Kikuchi K, Sameshima H, Hashiguchi T, Maruyama I
  • Journal Title: Biochem Biophys Res Commun 387 Pages: 42-46
• [Journal Article] Matrix Metalloproteinase-3 Accelerates Wound Healing Following Dental Pulp Injury (2009)
  • Author(s): Zheng L, Amano K, Iohara K, Ito M, Imabayashi K, Into T, Matsushita K, Nakamura H, Nakashima M
  • Journal Title: Am J Pathol 175 Pages: 1905-1914
• [Journal Article] Degradation of vascular endothelial thrombomodulin by arginine and lysine-specific cysteine proteases from Porphyromonas gingivalis (2009)
  • Author(s): Inomata M, Ishihara Y, Matsuyama T, Imamura T, Maruyama I, Noguchi T, Matsushita K
  • Journal Title: J Periodontol 80 Pages: 1511-1517
• [Journal Article] IL-4 alters expression patterns of storage components of vascular endothelial cell-specific granules through STAT6-and SOCS-1-dependent mechanisms. (2009)
  • Author(s): Inomata M, Into T, Nakashima M, Noguchi T, Matsushita K
  • Journal Title: Mol Immunol 46 Pages: 2080-2089
• [Journal Article] Aldosterone activates endothelial exocytosis (2009)
  • Author(s): §Jeong Y, Chaupin DF, §Matsushita K, Yamakuchi M, Cameron S, Morell CN, Lowenstein CJ
  • Journal Title: Proc Natl Acad Sci USA 106 Pages: 3782-3787
• [Journal Article] Regeneration of dental pulp after pulpotomy by transplantation of CD31(-)/CD146(-) side population cells from a canine tooth (2009)
  • Author(s): Iohara K, Zheng L, Ito M, Ishizaka R, Nakamura H, Into T, Matsushita K, Nakashima M
  • Journal Title: Regen Med 4 Pages: 377-385
• [Journal Article] IL-4 alters expression patterns of storage components of vascular endothelial cell-specific granules through STAT6-and SOCS-1-dependent mechanisms (2009)
  • Author(s): Inomata M, Into T, Nakashima M, Noguchi T, Matsushita K
  • Journal Title: Molecular Immunology (印刷中)
  • Peer Reviewed
• [Journal Article] Aldosterone activates endothelial exocytosis (2009)
  • Author(s): Jeong Y, Chaupin DF, Matsushita K, Yamakuchi M, Cameron S, Morell CN, Lowenstein CJ
  • Journal Title: Proc Natl Acad Sci USA 106 Pages: 3782-3787
  • Peer Reviewed
• [Journal Article] Degradation of vascular endothelial thrombomodulin by arginine and lysine-specific cysteine proteases from Porphyromonas gingivalis (2009)
  • Author(s): Inomata M, Ishihara Y, Matsuyama T, Imamura T, Maruyama I, Noguchi T, Matsushita K
  • Journal Title: Journal of Periodontology (印刷中)
  • Peer Reviewed
• [Journal Article] A Novel Stem Cell Source for Vasculogenesis in Ischemia: Subfraction of Side Population Cells from Dental Pulp (2008)
  • Author(s): Iohara K, Zheng L, Wake H, Ito M, Nabekura J, Wakita H, Nakamura H, Into T, Matsushita K, Nakashima M
  • Journal Title: Stem Cells 26 Pages: 2408-2418
• [Journal Article] The Role of Water Channel Aquaporin 3 in the Mechanism of TNF-Mediated Proinflammatory Events: Implication in Periodontal Inflammation (2008)
  • Author(s): Tancharoen S, Matsuyama T, Abeyama K, Matsushita K, Kawahara K, Sangalungkarn V, Tokuda M, Hashiguchi T, Maruyama I, Izumi Y
  • Journal Title: J Cell Physiol 217 Pages: 338-349
• [Journal Article] Regulation of MyD88-dependent signaling events by S nitrosylation retards toll-like receptor signal transduction and initiation of acute-phase immune responses (2008)
  • Author(s): Into T, Inomata M, Nakashima M, Shibata K, Hacker H, Matsushita K
  • Journal Title: Mol Cell Biol 28 Pages: 1338-1347
• [Journal Article] Nitric oxide regulates vascular calcification by interfering with TGF-signaling (2008)
  • Author(s): Kanno Y, Into T, Lowenstein CJ, Matsushita K
  • Journal Title: Cardiovasc Res 77 Pages: 221-730
• [Journal Article] Regulation of MyD88-dependent signaling events by S nitrosylation retards toll-like receptor signal transduction and initiation of acute-phase immune responses. (2008)
  • Author(s): Into T, Inomata M, Nakashima M, Shibata K, Hacker H, Matsushita K.
  • Journal Title: Mol Cell Biol 28 Pages: 1338-1347
  • Peer Reviewed
• [Journal Article] Nitric oxide regulates vascular calcification by interfering with TGF-signalling. (2008)
  • Author(s): Kanno Y, Into T, Lowenstein CJ, Matsushita K.
  • Journal Title: Cardiovasc Res. 77 Pages: 221-230
  • Peer Reviewed
• [Journal Article] Arginine-specific gingipain A from Porphyromonas gingivalis induces Weibel-Palade body exocytosis and enhanced activation of vascular endothelial cells through protease-activated receptors (2007)
  • Author(s): Inomata M, Into T, Ishihara Y, Nakashima M, Noguchi T, Matsushita K
  • Journal Title: Microbes Infect 9 Pages: 1500-1506
• [Journal Article] Roxithromycin inhibits tumor necrosis factor-alpha-induced matrix metalloproteinase-1 expression through regulating mitogen-activated protein kinase phosphorylation and Ets-1 expression (2007)
  • Author(s): Oyama T, Matsushita K, Sakuta T, Tokuda M, Tatsuyama S, Nagaoka S, Torii M
  • Journal Title: J Periodontal Res 42 Pages: 53-61
• [Journal Article] Pathogen recognition by Toll-like receptor 2 activates Weibel-Palade body exocytosis in human aortic endothelial cells (2007)
  • Author(s): Into T, Kanno Y, Dohkan JI, Nakashima M, Inomata M, Shibata KI, Lowenstein CJ, Matsushita K
  • Journal Title: J Biol Chem 282 Pages: 8134-8141
• [Journal Article] Runx3 negatively regulates Osterix expression in dental pulp cells (2007)
  • Author(s): Zheng L, Iohara K, Ishikawa M, Into T, Takano-Yamamoto T, Matsushita K, Nakashima M
  • Journal Title: Biochem J 405 Pages: 69-75
  • NAID: 10020162665
• [Journal Article] Synthesis and characterization of a dipalmitoylated lipopeptide derived from paralogous lipoproteins of Mycoplasma pneumoniae (2007)
  • Author(s): Into T, Dohkan J, Inomata M, Nakashima M, Shibata K, Matsushita K
  • Journal Title: Infect Immun 27 Pages: 2253-2259
• [Journal Article] Arginine-specific gingipain A from Porphyromonas gingivalis induces Weibel-Palade body exocytosis and enhanced activation of vasc ular endothelial cells through protease-activated receptors. (2007)
  • Author(s): Inomata M, Into T, Ishihara Y, Nakashima M, Noguchi T, Matsushita K.
  • Journal Title: Microbes Infect. 9 Pages: 1500-1506
  • Peer Reviewed
• [Journal Article] Synthesis and characterization of a dipalmitoylated lipopeptide derived from paralogous lipoproteins of Mycoplasma pneumoniae. (2007)
  • Author(s): Into T, Dohkan J, Inomata M, Nakashima M, Shibata K, Matsushita K.
  • Journal Title: Infect Immun 75 Pages: 2253-2259
  • Peer Reviewed
• [Journal Article] Pathogen recognition by Toll-like receptor 2 activates Weibel-Palade body exocytosis in human aortic endothelial cells. (2007)
  • Author(s): Into T, Kanno Y, Dohkan J, Nakashima M, Inomata M, Shibata K, Lowenstein CJ, Matsushita K.
  • Journal Title: J Biol Chem 282 Pages: 8134-8141
  • Peer Reviewed
• [Presentation] (2009)
  • Author(s): Amano K, Nakashima M, Zheng L, Iohara K, Matsui H, Yamasaki M, Matsushita K, Nakamura H
  • Organizer: Japanese Association for Dental Research
  • Place of Presentation: Nagoya
  • Year and Date: 2009-11-30
• [Presentation] 高齢者の様々な口腔保健行動が口腔状態に及ぼす影響 (2009)
  • Author(s): 坂下玲子、桑原未代子、松下健二、佐藤拓一、安彦友希、三重幸恵、井上昌一
  • Organizer: 第58回日本口腔衛生学会・総会
  • Place of Presentation: 岐阜
  • Year and Date: 2009-10-10
• [Presentation] E-selectinの新機能:感染の制御 (2009)
  • Author(s): 小松寿明、江口傑徳、杉浦進介、猪俣恵、古市保志、松下健二
  • Organizer: 日本歯科保存学会2009年度春季学術大会
  • Place of Presentation: 札幌
  • Year and Date: 2009-06-11
• [Presentation] たまねぎ外皮抽出物の調製とその抗動脈硬化・抗血栓作用 (2009)
  • Author(s): 位田毅彦, 二ノ宮真之, 纐纈守, 松下健二, 丸山征郎
  • Organizer: 第63回日本栄養・食糧学会大会
  • Place of Presentation: 長崎
  • Year and Date: 2009-05-20
• [Presentation] Th2由来サイトカインはSTAT6を介して血管内皮細胞特異的な分泌顆粒の構成因子の発現量を変化させる (2009)
  • Author(s): 猪俣恵, 引頭毅, 石原裕一, 松下健二, 野口俊英
  • Organizer: 第52回日本歯周病学会春季学術大会
  • Place of Presentation: 岡山
  • Year and Date: 2009-05-15
• [Presentation] 新規炎症性サイトカインHMGB1のアセチル化制御薬による放出制御 (2009)
  • Author(s): 杉浦進介, 江口傑徳, 猪俣恵, 小松寿明, 野口俊英, 松下健二
  • Organizer: 第52回日本歯周病学会春季学術大会
  • Place of Presentation: 岡山
  • Year and Date: 2009-05-15
• [Presentation] Aldosterone activates endothelial exocytosis (2009)
  • Author(s): Jeong Y, Chaupin DF, Matsushita K, Yamakuchi M, Cameron S, Morell CN, Lowenstein CJ
  • Organizer: The ATVB 2009 Annual Conference
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2009-04-29
• [Presentation] イチゴ品種"濃姫"と"美濃娘"の抗血栓作用 (2009)
  • Author(s): 安田雅晴、越川兼行、松下健二、纐纈守
  • Organizer: 園芸学会平成21年度春季大会
  • Place of Presentation: 東京
  • Year and Date: 2009-03-19
• [Presentation] Porphyromonas gingivalis is widely distributed in subgingival plaque biofilm of elderly people (2009)
  • Author(s): Abiko Y, Sato T, Matsushita K, Sakashita R, Takahashi N
  • Organizer: The 3rd International Symposium for Interface Oral Health Science
  • Place of Presentation: Sendai, Miyagi
  • Year and Date: 2009-01-15
• [Presentation] ヒストンアセチル化制御薬による新規炎症性サイトカインHMGB1の放出制御 (2008)
  • Author(s): 杉浦進介、江口傑徳、猪俣恵、小松寿明、野口俊英、松下健二
  • Organizer: BMB2008 (第31回日本分子生物学会年会・第81回日本生化学会大会合同大会)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] 可溶型セレクチンによる菌体成分排除 (2008)
  • Author(s): 江口傑徳、小松寿明、杉浦進介、猪俣恵、松下健二
  • Organizer: BMB2008 (第31回日本分子生物学会年会・第81回日本生化学会大会合同大会)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] Th1およびTh2由来サイトカインはSTATの活性化を介してWeibel-Palade Bodyの構成因子の発現を変化させる (2008)
  • Author(s): 猪俣恵、江口傑徳、杉浦進介、小松寿明、松下健二
  • Organizer: BMB2008(第31回日本分子生物学会年会・第81回日本生化学会大会合同大会)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] 乳歯由来歯髄細胞は血管新生・神経再生を促進する (2008)
  • Author(s): 庵原耕一郎、杉山昌彦、中村さやか、山田陽一、上田実、松下健二、中村洋、中島美砂子
  • Organizer: 第129回日本歯科保存学会
  • Place of Presentation: 富山
  • Year and Date: 2008-11-06
• [Presentation] エンドトキシンショック制御を目的としたHMGB1のアセチル化・放出の制御 (2008)
  • Author(s): 杉浦進介、江口傑徳、猪俣恵、小松寿明、松下健二
  • Organizer: 第14回日本エンドトキシンショク研究会
  • Place of Presentation: 仙台
  • Year and Date: 2008-10-25
• [Presentation] Arginine-specific gingipain A from Porphyromonas gingivalis induces Weibel-Palade body exocytosis and enhanced activation of vascular endothelial cells through protease-activated receptors (2008)
  • Author(s): Inomata M, Into T, Ishihara Y, Matsushita K, Noguchi T
  • Organizer: The 94th annual meeting of the American Academy of Periodontology
  • Place of Presentation: Seatle, USA
  • Year and Date: 2008-09-08
• [Presentation] Arginine-specific gingipain A from Porphyromonas gingivalis induces Weibel-Palade body exocytosis and enhanced activation of vascular endothelial cells through protease-activated receptors (2008)
  • Author(s): Inomata M, Into T, Ishihara Y, Matsushita K, Noguchi T
  • Organizer: The 94th annual meeting of the American Academy of Periodontology
  • Place of Presentation: Lake Tahoe, California, USA
  • Year and Date: 2008-09-08
• [Presentation] よく老いるための歯周病学のすすめ (2008)
  • Author(s): 松下健二
  • Organizer: 第8回日本抗加齢医学会総会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2008-06-07
• [Presentation] 高い血管新生能を有する歯髄CD31陰性SP細胞による歯髄再生 (2008)
  • Author(s): 庵原耕一郎、鄭力、和気弘明、伊藤正孝、鍋倉淳一、脇田英明、中村洋、引頭毅、松下健二、中島美砂子
  • Organizer: 第7回日本再生医療学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-03-13
• [Presentation] A Potential New Cell Source for Vasculogenesis in Ischemia, CD31-;CD146- Side Population Cells from Dental Pulp (2007)
  • Author(s): Nakashima M, Iohara K, Zheng L, Wake H, Ito M, Wakita H, Nabekura J, Nakamura H, Into T, Matsushita K
  • Organizer: The American Society for Cell Biology 47th Annual Meeting
  • Place of Presentation: Washington, DC, USA
  • Year and Date: 2007-12-04
• [Presentation] 高い血管新生能を有する歯髄CD31陰性SP細胞を用いた歯髄再生 (2007)
  • Author(s): 庵原耕一郎、中村洋、松下健二、中島美砂子
  • Organizer: 日本歯科保存学会2007年度秋季大会
  • Place of Presentation: 岡山
  • Year and Date: 2007-11-08
• [Presentation] Nitric oxide controls Toll-like receptor signal transduction through a redox-sensitive modification of MyD8 (2007)
  • Author(s): Into T, Inomata M, Nakashima M, Shibata K, Matsushita K
  • Organizer: The 7th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awaji, Japan
  • Year and Date: 2007-09-04
• [Presentation] Arginine-specific gingipain A from Porphyromonas gingivalis induces Weibel-Palade body exocytosis and enhanced activation of vascular endothelial cells through protease-activated receptors (2007)
  • Author(s): Inomata M, Into T, Nakashima M, Noguchi T, Matsushita K
  • Organizer: The 7th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awaji, Japan
  • Year and Date: 2007-09-04
• [Presentation] Gingipainはprotease-activated receptorの活性化を介してWeibel-Palade小体のエキソサイトーシスを誘導し、血管内皮細胞の炎症応答を増強する (2007)
  • Author(s): 猪俣恵、引頭毅、中島美砂子、野口俊英、松下健二
  • Organizer: 第49回歯科基礎医学会学術大会
  • Place of Presentation: 札幌
  • Year and Date: 2007-08-30
• [Presentation] Gingipainはprotease-activated receptorの活性化を介して Weibel-Palade小体のエキソサイトーシスを誘導し、血管 内皮細胞の炎症応答を増強する (2007)
  • Author(s): 猪俣 恵、引頭 毅、中島 美砂子、野口 俊英、松下 健二
  • Organizer: 第49回歯科基礎医学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2007-08-30
• [Presentation] 血管病としての歯周病の分子病態 (2007)
  • Author(s): 松下 健二
  • Organizer: 第49回歯科基礎医学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2007-08-29
• [Presentation] Runx3は歯髄細胞においてOsterixの発現を抑制する (2007)
  • Author(s): 鄭力、庵原耕一郎、松下健二、中島美砂子
  • Organizer: 日本歯科保存学会2007年度春季大会
  • Place of Presentation: 埼玉
  • Year and Date: 2007-06-08
• [Presentation] Gingipainはprotease-activated receptorの活性化を介してWeibel-Palade小体のエキソサイトーシスを誘導し、血管内皮細胞の炎症応答を増強する (2007)
  • Author(s): 猪俣恵、引頭毅、中島美砂子、野口俊英、松下健二
  • Organizer: 第50回日本歯周病学会春季学術大会
  • Place of Presentation: 横須賀
  • Year and Date: 2007-05-18
• [Book] Interface Oral Health Science 2009(Ed. Sasano T , Suzuki O, Porphyromonas gingivalis is widely distributed in subgingival plaque biofilm of elderly subjects, 3) (2010)
  • Author(s): Abiko Y, Sato T, Matsushita K, Sakashita R, Takahashi N
• [Book] Advances in Aging and Health Research 2009(高齢者の口腔・歯科疾患と免疫能 高齢者の口腔機能とケア) (2010)
  • Author(s): 松下健二(分担執筆)
  • Publisher: 財団法人長寿科学振興財団
• [Book] Exocytosis of Endothelial Cells is Regulated by N-ethylmaleimide Sensitive Factor(Ed Andrei Ivanov, 40) (2008)
  • Author(s): Yamakuchi M, Ferlito M, Morrell CN, Matsushita K, Fletcher CA, Cao W, Lowenstein CJ
  • Publisher: Methods in Molecular Biology
• [Book] Xa阻害剤のすべて(Xa因子の細胞生理活性) (2007)
  • Author(s): 松下健二(分担執筆)
  • Publisher: 先端医学社
• [Remarks]
  • URL: http://www.ncgg.go.jp/department/odr/index.html