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Inhibition of tissue-reparing signaling by P.gingivalis infection

Research Project

Project/Area Number 15390645
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Periodontal dentistry
Research InstitutionOsaka University

Principal Investigator

OKAHASHI Nobuo  Osaka University, Graduate School of Dentistry, Associate Professor, 大学院・歯学研究科, 助教授 (40150180)

Co-Investigator(Kenkyū-buntansha) AMANO Atsuo  Osaka University, Graduate School of Dentistry, Professor, 大学院・歯学研究科, 教授 (50193024)
NAKAGAWA Ichiro  Osaka University, Graduate School of Dentistry, Assistant Professor, 大学院・歯学研究科, 講師 (70294113)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2003: ¥6,000,000 (Direct Cost: ¥6,000,000)
Keywordsperiodontitis / tissue regeneration / P.gingivalis / cellular attachment / epithelial cells / periodontal ligament cells / 骨芽細胞
Research Abstract

P.gingivalis, a periodontopathic Gram-negative bacteria, is known to invade into a variety of host cells such as epithelial cells and fibroblasts. A chronic inflammation of infected periodontal tissue results in tissue destruction. In this study, we investigated the involvement of the two major virulent factors of this pathogen ; fimbriae and a protease called gingipain on the destruction and inhibition of regeneration of infected host tissues.
At first, we constructed fimbriae-deficient and gingipain-deficient mutants of P.gingivalis. Using these two mutants, we found that :
1)Both fimbriae- and gingipain-deficient mutants of P.gingivalis showed decreased invasion in human periodontal ligament cells (PDLs).
2)Infection of wild type of P.gingivalis in serum-free medium resulted in a detachment of PDLs from the culture dishes. However, gingipain-deficient mutant did not induce such detachment of PDLs.
3)Infection of wild type of P.gingivalis induced a degradation of integrin-associated signaling molecules such as FAK and paxillin. However, the degradation of FAK and paxillin was not observed during infection with gingipain-deficient mutant.
4)By using a scratch assay, we found that the infection of P.gingivalis strongly inhibited the regeneration of damaged monolayers of PDLs. The bacterial infection inhibited the cellular movement as well as the cellular growth.
5)Gingipain-deficient mutant did not show the inhibitory effect on the regeneration of the infected cellular monolayers. On the other hand, fimbriae-deficient mutant did inhibit the regeneration process.
These results strongly suggested that gingipain of P.gingivalis plays an important role in the inhibition of regeneration of the infected periodontal tissues.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (22 results)

All 2004 Other

All Journal Article (16 results) Publications (6 results)

  • [Journal Article] Porphyromonas gingivalis induces receptor activator of NF-kB ligand expression in osteoblasts through the activator protein-1 pathway.2004

    • Author(s)
      Okahashi N, Inaba H, Nakagawa I, Yamamura T, Kuboniwa M, Nakayama K, Hamada S, Amano A
    • Journal Title

      Infection and Immunity 72

      Pages: 1706-1714

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Variations of Porphyromonas gingivalis fimbriae in relation to microbial pathogenesis.2004

    • Author(s)
      Amano A, Nakagawa I, Okahashi N, Hamada S
    • Journal Title

      Journal of Periodontal Research 39

      Pages: 136-142

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Quantitative detection of periodontal pathogens using real-time polymerase chain reaction with TaqMan probe2004

    • Author(s)
      Kuboniwa M, Amano A, Kimura RK, Sekine S, Kato S, Yamamoto Y, Okahashi N, Iida T, Shizukuishi S
    • Journal Title

      Oral Microbiology and Immunology 19

      Pages: 168-176

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Comparison of inflammatory changes caused by Porphyromonas gingivalis with distinct fimA genotypes in a mouse abscess model.2004

    • Author(s)
      Nakano K, Kuboniwa M, Nakagawa I, Yamamura Y, Nomura R, Okahashi N, Ooshima T, Amano, A
    • Journal Title

      Oral Microbiology and Immunology 19

      Pages: 205-209

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of enamel matrix derivative on periodontal ligament cells diminished by Porphyromonas gingivalis2004

    • Author(s)
      Inaba H, Kawai S, Nakayama K, Okahashi N, Amano A
    • Journal Title

      Journal of Periodontology 75

      Pages: 865-872

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Autophagy defends cells against invading group A streptococci2004

    • Author(s)
      Nakagawa I, Amano A, Mizushima N, Yamamoto A, Yamaguchi H, Kamimoto T, Nara A, Funao J, Nakata M, Tsuda K, Hamada S, Yoshimori T
    • Journal Title

      Science 306

      Pages: 1037-1040

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Porphyromonas gingivalis induces receptor activator of NF-kB ligand expression in osteoblasts throuhg the activator protein-1 pathway.2004

    • Author(s)
      Okahashi, N., Inaba, H., Nakagawa, I., Yamamura, T., Kuboniwa, M., Nakayama, K., Hamada, S., Amano, A.
    • Journal Title

      Infection and Immunity 72

      Pages: 1706-1714

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Variations of Porphyromonas gingivalis fimbriae in relation to microbial pathogenesis.2004

    • Author(s)
      Amano, A., Nakagawa, I.Okahashi, N., Hamada, S.
    • Journal Title

      Journal of Periodontal Research 39

      Pages: 136-142

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Quantitative detection of periodontal pathogenesis using real-time polymerase chain reaction with TaqMan probe.2004

    • Author(s)
      Kuboniwa, M., Amano, A., Kimura, R.K., Sekine, S., Kato, S., Yamamoto, Y., Okahashi, N., Iida, T., Shizukuishi, S.
    • Journal Title

      Oral Microbiology and Immunology 19

      Pages: 168-176

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Comparison of inflammatory changes caused by Porphyromonas gingivalis with distinct fimA genotypes in a mouse abscess model.2004

    • Author(s)
      Nakano, K., Kuboniwa, M., Nakagawa, I., Yamamura, T., Nomura, R., Okahashi, N., Ooshima, T., Amano, A.
    • Journal Title

      Oral Microbiology and Immunology 19

      Pages: 205-209

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of enamel matrix derivative on periodontal ligament cells diminished by Porphyromonas gingivalis.2004

    • Author(s)
      Inaba, H., Kawai, S., Nakayama, K., Okahashi, N., Amano, A.
    • Journal Title

      Journal of Periodontology 75

      Pages: 865-872

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Autophagy defends cells against invading group A streptococcus.2004

    • Author(s)
      Nakagawa, I., Amano, A., Mizushima, N., Yamamoto, A., Yamaguchi, H., Kamimoto, T., Nara, A., Funao, J., Nakata, M., Tsuda, K., Hamada, S., Yoshimori, T.
    • Journal Title

      Science 306

      Pages: 1037-1040

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Porphyromonas gingivalis induces receptor activator of NF-kB ligand expression in osteoblasts through the activator protein a pathway.2004

    • Author(s)
      Okahashi N, Inaba H, Nakagawa I, Yamamura T, Kuboniwa M, Nakayama K, Hamada S, Amano A
    • Journal Title

      Infection and Immunity 72

      Pages: 1706-1714

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Quantitative detection of periodontal pathogens using real-time polymerase chain reaction with TaqMan probe2004

    • Author(s)
      Kuboniwa M, Amano A, Kimura RK, Sekine S, Kato S, Yamamoto Y, Okahashi N, Iida T.
    • Journal Title

      Oral Microbiology and Immunology 19

      Pages: 168-176

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Comparison of inflammatory changes caused by Porphyromonas gingivalis with distinct fimA genotypes in a mouse abscess model.2004

    • Author(s)
      Nakano K, Kuboniwa M, Nakagawa I, Yamamura Y, Nomura R, Okahashi N, Ooshima T, Amano A
    • Journal Title

      Oral Microbiology and Immunology 19

      Pages: 205-209

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Autophagy defends cells against invading group A streoptococc2004

    • Author(s)
      Nakagawa I, Amano A, Mizushima N, Yamamoto A, Yamaguchi H, Kamimoto T, Nara A, Funao J, Nakata M, Tsuda K, Hamada S, Yoshimori T
    • Journal Title

      Science 306

      Pages: 1037-1040

    • Related Report
      2004 Annual Research Report
  • [Publications] Itoh K, Udagawa N, Kobayashi K, Suda K, Li X, Takami M, Okahashi N, Nishihara T, Takahashi N.: "Lipopolysaccharide promotes the survival of osteoclasts via Toll-like receptor 4, but cytokine production of osteoclasts in response to lipopolysaccharide is different from that of macrophages"Journal of Immunology. 170. 3688-3695 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tani H, Limn CK, Yap CC, Onishi M, Nozaki M, Nishimune Y, Okahashi N, Kitagawa Y, Watanabe R, Mochizuki R, Moriishi K, Matsuura Y.: "In vitro and in vivo gene delivery by recombinant baculoviruses"Journal of Virology. 77. 9799-9808 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Okahashi N, Sakurai A, Nakagawa I, Fujiwara T, Kawabata S, Amano A, Hamada S.: "Infection by Streptococcus pyogenes induces the receptor activator of NF-kB ligand expression in mouse osteoblastic cells"Infection and Immunity. 71. 948-955 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakagawa I, Kurokawa K, Yamashita A, Nakata M, Tomiyasu Y, Okahashi N, Kawabata S, Yamazaki K, Shiba T, Yasunaga T, Hayashi H, Hattori M, Hamada S.: "Genomic sequence of an M3 strain of Streptococcus pyogenes reveals a large scale genomic rearrangement in invasive strains and new insights into phage evolution"Genome Research. 13. 1042-1055 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sakurai A, Okahashi N, Nakagawa I, Kawabata S, Amano A. Ooshima T, Hamada S.: "Streptococcus pyogenes infection induces septic arthritis with increased production of receptor activator of NF-kB ligand"Infection and Immunity. 71. 6019-6026 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakano K, Nomura R, Nakagawa I, Hamada S, Ooshima T.: "Determination of Streptococcus mutans with a cell wall polysaccharide specific to a new serotype k, in the human oral cavity"Journal of Clinical Microbiology. 42. 198-202 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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