2007 Fiscal Year Final Research Report Summary
Molecular Mechanisms of Interaction between Periodontitis and Cardiovascular and Bone Metabolic Disorders
| Project/Area Number |
17209057
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Nagasaki University |
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Principal Investigator |
NAKAYAMA Koji Nagasaki University, Graduate School of Biomedical Sciences, Professor (80150473)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Toru Nagasaki University, Graduate School of Biomedical Sciences, Professor (00211029)
YOSHMURA Atsutoshi Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor (70253680)
SAKAI Eiko Nagasaki University, Graduate School of Biomedical Sciences, Assistant Professor (10176612)
NAITO Mariko Nagasaki University, Graduate School of Biomedical Sciences, Assistant Professor (20244072)
AMANO Atsuo Osaka University, Graduate School of Dental Science, Professor (50193024)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Infectious Disease / Bacteria / Dental Science / Circulation ・ High Blood Pressure / Immunoloey |
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| Research Abstract |
The periodontopathic bacterium Porphyromonas gingivalis has the ability to agglutinate human erythrocytes. We found that the Hgp44 domain protein, which is encoded by gingipain-related genes of P. gingivalis, can agglutinate erythrocytes by using a recombinant Hgp44 protein. The target molecule on the cell surface of erythrocytes against Hgp44 was found to be glycophorin. Also, we found that a peptide encoded by a DNA region backward of the region encoding Hgp44 has the inhibitory effect on the Hgp44-mecliated hemagglutination.
P. gingivalis cell-induced platelet aggregation is particularly important for interaction between periodontal disease and cardiovascular disease. It has been believed that P. gingivalis-mediated platelet aggregation is caused by activation of PAR receptor on platelets by Arg-gingipain. However, we found that P. gingivalis cell-mediated platelet aggregation does not depend on Arg-gingipain but Hgp44 protein on the bacterial cell surface, anti-P. gingivalis antibody in serum, and FcγRIIa and GPIlb/IIIa on platelets.
Alveolar bone resorption is one of the characteristic symptoms in periodontal disease, which results in tooth loss. Tooth loss causes loss of the gingival crevice that is an anatomical niche for periodontal pathogens such as P. gingivalis. We found that culture supernatants of P. gingivalis have the ability to inhibit in vitro osteoclastogenesis from bone marrow macrophages and determined that a hemoglobin receptor protein (HbR), which is a major protein in the culture supernatants, is the inhibitor to osteoclast formation. The HbR protein inhibited RANKL-induced Akt phosphorylation and expression of NFATc1 and c-Fos.
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[Journal Article] Molecular analysis of RANKL-independent cell fusion of osteoclast-like cells induced by TNF-□, lipopolysaccharide, or peptidoglycan2007
Author(s)
Hotokezaka, H., Sakai, E., Ohara, N., Hotokezaka, Y., Gonzales, C., Matsuo, K., Fujimura, Y., Yoshida, N., Nakayama, K.
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Journal Title
J. Cell. Biochem 101(1)
Pages: 122-134
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cnstruction of recombinant hemagglutinin derived from the gingipain-encoding gene of Porphyromonas gingivalis, identification of its target protein on erythrocytes, and inhibition of hemagglutination by an inter-domain regional peptide2007
Author(s)
Sakai, E., Naito, M., Sato, K., Hotokezaka, H., Kadowaki, T., Kamaguchi, A., Yamamoto, K., Okamoto, K., Nakayama, K.
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Journal Title
J. Bacteriol 189(11)
Pages: 3977-3986
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Porphyromonas gingivalis-induced platelet aggregation in plasma depends on Hgp44 adhesin but not Rgp proteinase2006
Author(s)
Naito, M., Sakai, E., Shi, Y., Ideguchi, H., Shoji, M., Ohara, N., Yamamoto, K., Nakayama, K.
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Journal Title
Mol. Microbiol 59
Pages: 152-167
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Gingipains inactivates a cell surface ligand on Porphyromonas gingivalis that induces TLR2- and TLR4-independent signaling2006
Author(s)
Kishimoto, M., Yoshimura, A., Naito, M., Okamoto, K., Yamamoto, K., Golenbock, D.T., Hara, Y. Nakayama, K.
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Journal Title
Microbiol. Immunol 50(4)
Pages: 315-325
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Analysis of amphotericin B-Induced cell signaling with chemical inhibitors of signaling molecules2006
Author(s)
Matsuo, K., Hotokezaka, H., Ohara, N., Fujimura, Y., Yoshimura, A., Okada, Y., Hara, Y., Yoshida, N., Nakayama, K.
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Journal Title
Microbiol. Immunol 50(4)
Pages: 337-347
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hemoglobin receptor protein(HbR) of Porphyromonas gingivalis inhibits receptor activator NF-□B ligand-induced osteoclastogenesis from bone marrow macrophages2006
Author(s)
Fujimura, Y., Hotokezaka, H., Ohara, N., Naito, M., Sakai, E., Yoshimura, M., Narita, Y., Kitaura, H., Yoshida, N., Nakayama, K.
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Journal Title
Infect. Immun 74(5)
Pages: 2544-2551
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Temporal activation of anti-and pro-apoptotic factors in human gingival fibroblasts infected with the periodontal pathogen, Porphyromonas gingivalis : potential role of bacterial proteases in host signalling2006
Author(s)
Urnowey, S., Ansai, T., Bitko, V., Nakayama, K., Takehara, T., Barik, S.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] IL-18 induces apoptosis of adherent bone marrow cells in TNF-alpha mediated osteoclast formation in synergy with IL-12.2006
Author(s)
Kitaura, H., Tatamiya, M., Nagata, N., Fujimura, Y., Eguchi, T., Yoshida, N., Nakayama, K.
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Journal Title
Immunol. Lett. 107(1)
Pages: 22-31
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Crystal structure and mechanism of tripeptidyl activity of prolyl tripeptidyl aminopeptidase from Porphyromonas gingivalis2006
Author(s)
Ito, K., Nakajima, Y., Xu, Y., Yamada, N., Onohara, Y., Matsubara, F., Kabashima T., Nakayama, K., Yoshimoto, T.
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Journal Title
J. Mol. Biol. 362
Pages: 228-240
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Identification of a new membrane-associated protein which influences transport/maturation of gingipains and adhesins of Porphyromonas gingivalis2005
Author(s)
Sato, K., Sakai, E., Veith, P.D., Shoji, M., Kikuchi, Y., Yukitake, H., Ohara, N., Naito, M., Okamoto, K., Reynolds, E.C., Nakayama, K.
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Journal Title
J. Biol. Chem. 280(10)
Pages: 8668-8677
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Novel stationary-phase-upregulated protein ・ of Porphyromonas gingivalis influences the production of superoxide dismutase, thiol perxidase and thioredoxin2005
Author(s)
Kikuchi, Y., Ohara, N., Sato, K., Yoshimura, M., Yukitake, H., Sakai, E., Shoji, M., Naito, M., Nakayama, K.
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Journal Title
Microbiology 151
Pages: 841-853
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The antibacterial surface of dental implants based on the photocatalytic bactericidal effect2005
Author(s)
Suketa, N., Sawase, T., Kitaura, H., Naito, M., Baba, K., Nakayama, K., Wennerberg, A., Atsuta, M.
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Journal Title
Clin. Implant Dent. Relat. Res. 7
Pages: 105-111
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Arginine-specific gingipains from Porphyromonas gingivalis stimulate production of hepatocyte growth factor(scatter factor) through protease-activated receptors in human gingival fibroblasts in culture2005
Author(s)
Uehara, A., Muramoto, K., Imamura, T., Nakayama, K., Potempa, J., Travis, J., Sugawara, S., Takada, H.
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Journal Title
J. Immunol. 175
Pages: 6076-6084
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Functional expression of lysine-specific cysteine proteinase(Lys-gingipain) by a Porphyromonas gingivalis plasmid system
Author(s)
Ishida, Y., Hu, J-P., Sakai, E., Kadowaki, T., Yamamoto, K., Tsukuba, T., Nakayama, K., Okamoto, K.
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Journal Title
Arch. Oral Biol. (In press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Dual regulation of IL-8 production in human oral epithelial cells upon stimulation with gingipains from Porphyromonas gingivalis
Author(s)
Uehara, A., Naito, M., Imamura, T., Potempa, J., Travis, J., Nakayama, K., Takada, H.
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Journal Title
J. Med. Microbiol (In press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Proteome analysis of Porphyromonas gingivalis cells placed in a subcutaneous chamber of mice
Author(s)
Yoshimura, M., Ohara, N., Kondo, Y., Shoji, M., Okano, S., Nakano, Y., Abiko, Y., Nakayama, K.
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Journal Title
Oral Microbiol. Immunol (In press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Involvement of a tetratricopeptide repeat-containing protein in the virulence of Porphyromonas gingivalis
Author(s)
Kondo, Y., Yoshimura, M., Ohara, N., Shoji, M., Yukitake, H., Naito, M., Fujiwara, T., Nakayama, K.
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Journal Title
Interface Oral Health Science (in press)
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Characterization of the hbp35 gene products in Porphyromonas gingivalis2007
Author(s)
Shoji, M., Shibata, Y., Shiroza, T., Yukitake, H., Peng, B., Naito, M., Dashper, S., Abiko, Y., Nakayama, K., Reynolds, EC.
Organizer
The BacPath 9 meeting for Australian Society for Microbiology in Lorne
Place of Presentation
Victoria, Australia
Year and Date
20070000
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Diverse effects of BCG infection on various stages of RANKL-induced osteoclast differentiation2006
Author(s)
Ohara, N., Yoshimura, M., Shoji, M., Kondo, Y., Nakayama, K.
Organizer
Forty-first Joint Research Conference on Leprosy and Tuberculosis : The United State-Japan Cooperative Medical Science Program
Place of Presentation
Kagoshima, Japan
Year and Date
20060000
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Bacterial infection inhibits osteoclastogenesis in vitro2005
Author(s)
Ohara, N., Yoshimura, M., Saito, K., Hotokezaka, H., Nakayama, K.
Organizer
11th International Congress of Bacteriology and Applied Microbiology Division, Joint Meeting of the 3 Divisions of the International Union of Microbiological Societies 2005
Place of Presentation
San Francisco, U.S.A.
Year and Date
20050000
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Effects of water-soluble chitosan on invasion of Porphyromonas gingivalis2005
Author(s)
Ohara, N., Ohara, N., Yoshimura, M., Ganno, T., Yamada, S., Nakayama, K., Hayashi, Y.
Organizer
11th International Congress of Bacteriology and Applied Microbiology Division, Joint Meeting of the 3 Divisions of the International Union of Microbiological Societies 2005
Place of Presentation
San Francisco, U.S.A.
Year and Date
20050000
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Characterization of the HBP35-deficient mutants of Porphyromonas gingivalis
Author(s)
Shoji, M., Shibata, Y., Shiroza, T., Yukitake, H., Abiko, Y., Nakayama, K.
Organizer
84th General Session & Exihibition of the IADR
Place of Presentation
Brisbane, Australia
Description
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