Molecular mechanism involved in the association of periodontal disease with pathology of metabolic syndrome

• Project/Area Number: 19209064
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Social dentistry
• Research Institution: Osaka University
• Principal Investigator: SHIZUKUISHI Satoshi Osaka University, 大学院・歯学研究科, 教授 (00028789)
• Co-Investigator(Kenkyū-buntansha): OTSUKI Michio 大阪大学, 医学系研究科, 助教 (00403056) ; TANAKA Muneo 大阪大学, 歯学部附属病院, 講師 (90263300) ; KUBONIWA Masae 大阪大学, 大学院・歯学研究科, 助教 (00303983) ; SEKINE Shinichi 大阪大学, 大学院・歯学研究科, 助教 (70506344) ; 片岡 宏介 大阪大学, 歯学研究科, 助教 (50283792)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥50,050,000 (Direct Cost: ¥38,500,000、Indirect Cost: ¥11,550,000); Fiscal Year 2009: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2008: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000); Fiscal Year 2007: ¥30,160,000 (Direct Cost: ¥23,200,000、Indirect Cost: ¥6,960,000)
• Keywords: メタボリックシンドローム / 歯周病 / 疫学 / 分子生物学 / 歯周病原性細菌歯肉上皮細胞 / バイオフィルム / Porphyromonas gingivalis / Fusobacterium nucleatum / 免疫 / 糖尿病 / 血清脂質異常 / 炎症性サイトカイン / 動脈硬化性疾患 / 動物モデル / 歯周病細菌 / 肥満 / 血圧高値 / 空腹時血糖 / 循環器疾患 / バイオマーカー

Research Abstract

The purpose of this investigation was to examine the association of periodontal disease and various components of metabolic syndrome. In epidemiological studies, high blood pressure and periodontitis were significantly associated with macrovascular disease(s) as risk indicators. Levels of the inflammatory biomarkers including ICAM in the subjects with periodontitis increased meaningfully in comparison with the subjects without periodontitis. In apolipoprotein E-deficient mice, high-cholesterol diet and infection with Porphyromonas gingivalis accelerated inflammatory cytokines and atherosclerosis. Furthermore, a series of in vitro infection studies revealed that a periodontal pathogen caused cell cycle dysregulation in gingival epithelial cells.

Research Products

• [Journal Article] Fusobacterium nucleatum envelope protein FomA is immunogenic and binds to the salivary statherin-derived peptide. (2010)
  • Author(s): Nakagaki, H. Sekine, S., Terao, Y., Toe, M., Tanaka, M., Ito, H.O., Kawabata, S., Shizukuishi, S., Fujihashi. K., Kataoka, K.
  • Journal Title: Infection and Immunity 78 Pages: 1185-1192
  • Peer Reviewed
• [Journal Article] Association of ALDH2 genotypes with periodontitis progression. (2010)
  • Author(s): Nishida, N., Tanaka, M., Sekine, S., Takeshita, T., Nakayama, K., Morimoto, K., Shizukuishi, S.
  • Journal Title: Journal of Dental Research 89 Pages: 138-142
  • Peer Reviewed
• [Journal Article] Fusobacterium nucleatum envelope protein FomA is immunogenic and binds to the salivary statherin-derived peptide. (2010)
  • Author(s): Nakagaki, H.
  • Journal Title: Infection and Immunity 78 Pages: 1185-1192
  • Peer Reviewed
• [Journal Article] Assicuation of ALDH2 genotypes with periodontitis progression. (2010)
  • Author(s): Nashida, N.
  • Journal Title: Journal of Dental Research 89 Pages: 138-142
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): Kuboniwa, M., Amano, A., Hashino, E., Yamamoto, Y., Inaba, H., Hamada, N., Nakayama, K., Tribble, G.D., Lamont, R.J. Shizukuishi, S.
  • Journal Title: BMC Microbiol. 9 Pages: 105-105
  • Peer Reviewed
• [Journal Article] Homotypic biofilm structure of Porphyromonas gingivalis is affected by FimA type variations. (2009)
  • Author(s): Kuboniwa, M., Amano, A., Inaba, H., Hashino, E., Shizukuishi, S.
  • Journal Title: Oral Microbiol. Immunol. 24 Pages: 260-263
  • Peer Reviewed
• [Journal Article] Identification of binding domain of Streptococcus oralis glyceraldehyde-3-phosphate dehydrogenase for Porphyromonas gingivalis major fimbriae. (2009)
  • Author(s): Nagata, H., Iwasaki, M., Maeda, K., Kuboniwa, M., Hashino, E., Toe, M., Minamino, N., Kuwahara, H., Shizukuishi, S.
  • Journal Title: Infect. Immun. 77 Pages: 5130-5138
  • Peer Reviewed
• [Journal Article] Distinct roles of long/short fimbriae and gingipains in homotypic biofilm development by Porphyromonas gingivalis. (2009)
  • Author(s): Kuboniwa, M.
  • Journal Title: BMC Microbiology 9 Pages: 105-105
  • Peer Reviewed
• [Journal Article] Homotypic biofilm structure ofporphyromonas gingivalis is affected by FimA type variations. (2009)
  • Author(s): Kuboniwa, M.
  • Journal Title: Oral Microbiology and Immunology 24 Pages: 260-263
  • Peer Reviewed
• [Journal Article] Identification of binding domain of Streptococcus oralis glyceraldehyde-3-phosphate dehydrogenase for Porphyromonas gingivalis major fimbriae. (2009)
  • Author(s): Nagata, H.
  • Journal Title: Infection and Immunity 77 Pages: 5130-5138
  • Peer Reviewed
• [Journal Article] Homotypic biofilm structure of Porphyromonas gingivalis is affected by FimA type variations (2009)
  • Author(s): Kuboniwa, M
  • Journal Title: Oral Microbiology and Immunology 24(in press)
  • Peer Reviewed
• [Journal Article] P. gingivalis accelerates gingival epithelial cell progression through the cell cycle. (2008)
  • Author(s): Kuboniwa, M., Hasegawa, Y., Mao, S., Amano, A., Shizukuishi, S., Lamont, R.J., Yilmaz, O.
  • Journal Title: Microbes Infect 10 Pages: 122-128
  • Peer Reviewed
• [Journal Article] Relationship of Porphyromonas gingivalis with glycemic level in patients with type 2 diabetes following periodontal treatment. (2008)
  • Author(s): Makiura, N., Ojima, M., Kou, Y., Furuta, N., Okahashi, N., Shizukuishi, S., Amano, A.
  • Journal Title: Oral Microbiol. Immunol. 23 Pages: 348-351
  • Peer Reviewed
• [Journal Article] A novel adenovirus expressing Flt3 ligand enhances mucosal immunity by inducing mature NALT dendritic cell migration. (2008)
  • Author(s): Sekine, S., Kataoka, K., Fukuyama, Y., Adachi, Y., Davydova, J., Yamamoto, M., Kobayashi, R., Fujihashi, K., Suzuki, H., Curiel, D., Shizukuishi, S., McGhee, J., Fujihashi, K.
  • Journal Title: J. Immunol. 180 Pages: 8126-8134
  • Peer Reviewed
• [Journal Article] Association between involuntary smoking and salivary markers related to periodontitis: a 2-year longitudinal study. (2008)
  • Author(s): Nishida, N., Yamamoto, Y., Tanaka, M., Kataoka, K., Kuboniwa, M., Nakayama, K., Morimoto, K., Shizukuishi, S.
  • Journal Title: J. Periodontol. 79 Pages: 2233-2240
  • Peer Reviewed
• [Journal Article] 解明されつつあるメタボリックシンドロームと歯周病との関係 (2008)
  • Author(s): 田中宗雄, 雫石聰
  • Journal Title: 機器・試薬 31 Pages: 34-40
• [Journal Article] 歯周病と予防食品の開発. (2008)
  • Author(s): 雫石聰, 田中宗雄
  • Journal Title: 食品と開発 43 Pages: 4-6
• [Journal Article] Association between involuntary smoking and salivary markers related to periodontitis : a 2-year longitudinal study (2008)
  • Author(s): Nishida, N
  • Journal Title: Journal of Periodontology 79 Pages: 2233-2240
  • Peer Reviewed
• [Journal Article] Effect of eucalyptus extract chewing gum on periodontal health : a double-masked, randomized trial (2008)
  • Author(s): Nagata, H
  • Journal Title: Journal of Periodontology 79 Pages: 1378-1385
  • Peer Reviewed
• [Journal Article] 解明されつつあるメタボリツクシンドロームと歯周病との関係 (2008)
  • Author(s): 雫石 聰
  • Journal Title: 医療と検査機器・試薬 31 Pages: 34-40
• [Journal Article] 歯周病と予防食品の開発 (2008)
  • Author(s): 雫石 聰
  • Journal Title: 食品と開発 43 Pages: 4-6
• [Journal Article] 解明されつつあるメタボリックシンドロームと歯周病との関係 (2008)
  • Author(s): 田中宗雄, 雫石 聰
  • Journal Title: 医療と検査機器・試薬 31 Pages: 34-40
• [Journal Article] Longitudinal study of the association between smoking as a periodontitis risk and salivary biomarkers related to periodontitis. (2007)
  • Author(s): Kibayashi, M., Tanaka, M., Nishida, N., Kuboniwa, M., Kataoka, K., Nagata, H., Nakayama, K., Morimoto, K., Shizukuishi, S.
  • Journal Title: J. Periodontol. 78 Pages: 859-867
  • Peer Reviewed
• [Journal Article] Nasal cholera toxin elicits IL-5 and IL-5 receptor a chain expressing B-laB cells for innate mucosal IgA antibody responses. (2007)
  • Author(s): Kataoka, K., Fujihashi, K., Sekine, S., Fukuiwa, T., Kobayashi, R., Suzuki, H., Nagata, H., Takatsu, K., Shizukuishi, S., McGhee, J.R., Fujihashi, K.
  • Journal Title: J. Immunol. 178 Pages: 58-6065
  • Peer Reviewed
• [Journal Article] Longitudinal Study of the Association between Smoking as a Periodontitis Risk and Salivary Biomarkers Related to Periodontitis (2007)
  • Author(s): Kibayashi, M. Tanaka, M. Nishida, N. Kuboniwa, M. Kataoka, K. Nagata, H. Nakayama, K. Morimoto, K. Shizukuishi, S.
  • Journal Title: Journal of Periodontology 78 Pages: 859-867
  • Peer Reviewed
• [Journal Article] 口腔保健と健康寿命 (2007)
  • Author(s): 雫石 聰
  • Journal Title: 大阪大学医学部学友会会誌 27 Pages: 79-83
• [Presentation] Antigen presenting cell function of NALT DCs is maintained in aged mice. (2009)
  • Author(s): Sekine, S.
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2009-12-02
• [Presentation] 粘膜アジュバントとして用いたFlt3 ligand cDNA 及び CpG ODNの免疫誘導能解析 (2009)
  • Author(s): 関根伸一
  • Organizer: 第58回日本口衛生学会
  • Place of Presentation: 岐阜市
  • Year and Date: 2009-10-11
• [Presentation] High-cholesterol diet accelerates inflammatory cytokine production in apolipoprotein E-null mice infected with Porphyromonas gingivalis. (2009)
  • Author(s): Sekine, S.
  • Organizer: 14th International Congress of Mucosal Immunology
  • Place of Presentation: Boston, USA
  • Year and Date: 2009-07-06
• [Presentation] Association of inflammatory biomarkers with periodontitis in diabetic patients. (2009)
  • Author(s): Tanaka, M.
  • Organizer: 87th General Session & Exhibithion of the IADR
  • Place of Presentation: Miami, Fla., USA
• [Presentation] Periodontitis and components of metabolic syndrome in diabetic macrovascular risk. (2009)
  • Author(s): Tanaka, M.
  • Organizer: 87th General Session & Exhibithion of the IADR
  • Place of Presentation: Miami, USA
• [Presentation] Association between breath evaluation with electronic nose and serum biomarkers in diabetic patients. (2009)
  • Author(s): Tanaka, M.
  • Organizer: 8th Conference of ISBOR(BREATH2009)
  • Place of Presentation: Dortmund, Germany
• [Presentation] 粘膜アジュバントとして用いたFlt3 ligand cDNA及びCpG ODNの免疫誘導能解析. (2009)
  • Author(s): 関根伸一
  • Organizer: 58th日本口腔衛生学会・総会
  • Place of Presentation: Gifu
• [Presentation] Antigen Presenting Cell Function of NALT DCs Is Maintained in Aged Mice. (2009)
  • Author(s): Sekine, S.
  • Organizer: 39th日本免疫学会
  • Place of Presentation: Osaka
• [Presentation] Asociation between breath evaluation with electronic nose and serum biomarkers in diabetic patients. (2009)
  • Author(s): Tanaka, M
  • Organizer: 8th Conference of ISBOR
  • Place of Presentation: Dortmund, Germany
• [Presentation] 気管切開チューブ装着患者の下気道より検出される歯周病細菌の基礎的解析 (2008)
  • Author(s): 江間弘子
  • Organizer: 第4回ホロニクスグループ学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2008-12-14
• [Presentation] Porphyromonas gingivalis線毛への口腔レンサ球菌菌体表層glyceraldehyde-3-phosphate dehydrogenaseの結合部位の解析 (2008)
  • Author(s): 岩崎未央
  • Organizer: 大阪大学歯学会第106回例会
  • Place of Presentation: 吹田市
  • Year and Date: 2008-07-17
• [Presentation] 人工呼吸器装着患者の下気道より検出される歯周病細菌の基礎的解析 (2008)
  • Author(s): 上月弘子
  • Organizer: 第19回日本口腔衛生学会近畿・中国・四国地方会総会
  • Place of Presentation: 徳島市
  • Year and Date: 2008-06-22
• [Presentation] Distinct roles of major/minor fimbriae and gingipains in homotypic biofilm development by Porpyhromonas gingivalis. (2008)
  • Author(s): Kuboniwa, M.
  • Organizer: BiofilmsIII: 3rd International Conference
  • Place of Presentation: Munich, Germany
• [Presentation] NALT CD11b+ dendritic cell migration and balanced Th1- and Th2- cytokine responses induce antigen-specific immunity. (2008)
  • Author(s): Sekine, S.
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: Kyoto
• [Presentation] Role of Streptococcus gordonii Cbe protein in periodontopathic biofilm development. (2008)
  • Author(s): Kuboniwa, M
  • Organizer: 86th General session & exhibition of the IADR
  • Place of Presentation: Toronto, Canada
• [Presentation] Distinct roles of major/minor fimbriae and gingipains in homotypic biofilm development by Porphyromonas gingivalis (2008)
  • Author(s): Kuboniwa, M.
  • Organizer: Biofilms III : 3^<rd> International Conference
  • Place of Presentation: Munich, Germany
• [Presentation] High-cholesterol diet accelerates inflammatory cytokine production in apolipoprotein E-null mice infected with Porphyromonas gingivalis.
  • Author(s): Sekine, S.
  • Organizer: 14th ICMI
  • Place of Presentation: Boston (USA)
• [Presentation] 糖尿病患者における動脈硬化性疾患と歯周病の関連
  • Author(s): 笠山宗正
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京