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Molecular analysis of the interaction between immune function and bone metabolisms in periodontitis

Research Project

Project/Area Number 13470459
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Periodontal dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

ISHIKAWA Isao  Graduate School, Professor and chairman, 大学院・医歯学総合研究科, 教授 (10014151)

Co-Investigator(Kenkyū-buntansha) NOGUCHI Kazuyuki  Graduate School, Research Associate, 大学院・医歯学総合研究科, 助手 (90218298)
NITTA Hiroshi  Graduate School, Associate Professor, 大学院・医歯学総合研究科, 助教授 (70237767)
NAGASAWA Toshiyuki  Graduate School, Research Associate, 大学院・医歯学総合研究科, 助手 (90262203)
Project Period (FY) 2001 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2001: ¥6,800,000 (Direct Cost: ¥6,800,000)
Keywordsperiodontitis / RANKL / OPG / IL-1 / T-cell / プロスタグランジン / 破骨細胞 / 歯肉線維芽細胞 / プロスタグランジンE2 / ICAM-1
Research Abstract

Periodontopathic bacteria, immune responses and bone metabolisms were examined to clarify the interaction between immune responses and bone metabolisms in periodontitis. We have established the detection system for periodontopathic bacteria using real-time PCR analysis. Based on the system, we have found that periodontopathic bacteria were frequently detected in the surgically removed vessels from the cardio-vascular disease patients with periodontitis. In addition, monocytes from periodontitis patients were activated compared with healthy subjects. Serum IL-6 concentration was significantly elevated immediately after periodontal treatment. These results suggested that periodontitis might affect systemic health through bacteremia or production of inflammatory cytokines by activated monocytes. Bone metabolisms are regulated by osteoclasts and osteoblasts, and osteoclast differentiation is regulated by RANKL and OPG produced by osteoblasts. We have reported that RANKL expression was high in severe periodontitis lesion, and T-cells from periodontitis tissue expressed RANKL. Both periodontal ligament fibroblasts (PDL) and gingival fibroblasts produced OPG. IL-1 augmented RANKL expression in PDL five times higher than HGF, but OPG production was lower than HGF.

Report

(5 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (53 results)

All 2004 2003 2002 Other

All Journal Article (33 results) Book (1 results) Publications (19 results)

  • [Journal Article] Detection and localization of periodontopathic bacteria in abdominal aortic aneurysms.2004

    • Author(s)
      Kurihara N, Inoue Y, Iwai T, Umeda M, Huang Y, Ishikawa I.
    • Journal Title

      Eur J Vase Endovasc Surg 28・5

      Pages: 553-558

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Costimulation via Glucocorticoid-Induced TNF Receptor in Both Conventional and CD25+ Regulatory CD4+ T Cells.2004

    • Author(s)
      Kanamaru F, Youngnak P, Hashiguchi M, Nishioka T, Takahashi T, Sakaguchi S, Ishikawa I, Azuma M
    • Journal Title

      J Immunol 732・12

      Pages: 7306-7314

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Biological activities of Bacteroides forsythus lipoproteins and their possible pathological roles in periodontal disease2004

    • Author(s)
      Hasebe A, Yoshimura A, Into T, Kataoka H, Tanaka S, Arakawa S, Ishikura H, Golenbock DT, Sugaya T, Tsuchida N, Kawanami M, Hara Y, Shibata K
    • Journal Title

      Infect Immun 73・3

      Pages: 1318-1325

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prostagrandin E-2regulates interleukin-1 beta-induced matrix metalloproteinase-32004

    • Author(s)
      Ruwanpura SMPM, Noguchi K, Ishikawa I
    • Journal Title

      J Dent Res 83・4

      Pages: 260-265

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of CD14, CD16 and CD45RA on monocytes from periodontitis patients2004

    • Author(s)
      Nagasawa T, Kobayashi H, Aramaki M, Kiji M, Oda S, Izumi Y.
    • Journal Title

      J Periodontal Res 39・2

      Pages: 129-135

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Detection and localization of periodontopathic bacteria in abdominal aortic aneurysms2004

    • Author(s)
      Kurihara N, Inoue Y, Iwai T, Umeda M, Huang Y, Ishikawa I.
    • Journal Title

      Eur J Vasc Endovasc Surg 28

      Pages: 5553-5558

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Costimulation via Glucocorticoid-Induced TNF Receptor in Both Conventional and CD25+ Regulatory CD4+ T Cells2004

    • Author(s)
      Kanamaru F, Youngnak P, Hashiguchi M, Nishioka T, Takabashi T, Sakaguchi S, Ishikawa I, Azuma M
    • Journal Title

      J Immunol 732・12

      Pages: 7306-7314

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Biological activities of Bacteroides forsythus lipoproteins and their possible pathological roles in periodontal disease2004

    • Author(s)
      Hasebe A, Yoshimura A, Into T, Kataoka H, Tanaka S, Arakawa S, Ishikura H, Golenbock DT, Sugaya T, Tsuchida N, Kawanami M, Hara Y, Shibata K.
    • Journal Title

      Infect Immun 73・3

      Pages: 1318-1325

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prostaglandin E-2 regulates interleukin-1 beta-induced matrix metalloproteinase-32004

    • Author(s)
      Ruwanpura SMPM, Noguchi K, Ishikawa I
    • Journal Title

      J Dent Res 83・4

      Pages: 260-265

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Detection and localization of periodontopathic bacteria in abdominal aortic aneurysms.2004

    • Author(s)
      Kurihara N, Inoue Y, Iwai T, Umeda M, Huang Y, Ishikawa I
    • Journal Title

      Eur J Vasc Endovasc Surg 28・5

      Pages: 553-558

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Costimulation via Glucocorticoid-Induced TNF Receptor in Both Conventional and CD25+ Regulatory CD4+ T Cells.2004

    • Author(s)
      Kanamaru F, Youngnak P, Hashiguchi M, Nishioka T, Takahashi T, Sakaguchi S, Ishikawa I, Azuma M.
    • Journal Title

      J Immunol 732・12

      Pages: 7306-7314

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Biological activities of Bacteroides forsythus lipoproteins and their possible pathological roles in periodontal disease.2004

    • Author(s)
      Hasebe A, Yoshimura A, Into T, Kataoka H, Tanaka S, Arakawa S, Ishikura H, Golenbock DT, Sugaya T, Tsuchida N, Kawanami M, Hara Y, Shibata K.
    • Journal Title

      Infect Immun 73・3

      Pages: 1318-1325

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Prostagrandin E-2regulates interleukin-1 beta-induced matrix metalloproteinase-3 production in human gingival fibroblasts.2004

    • Author(s)
      Ruwanpura SMPM, Noguchi K, Ishikawa I.
    • Journal Title

      J Dent Res 83・4

      Pages: 260-265

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of CD14, CD16 and CD45RA on monocytes from periodontitis patients2004

    • Author(s)
      Nagasawa T, Kobayashi H, Aramaki M, Kiji M, Oda S, Izumi Y.
    • Journal Title

      J Periodontal Res 39・1

      Pages: 72-78

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effect of low dose Actinobacillus actinomycetemcomitans lipopolysaccharide pretreatment on cytokine production by human whole blood.2004

    • Author(s)
      Nakamura T, Nitta H, Ishikawa I.
    • Journal Title

      J Periodontal Res 39・2

      Pages: 129-135

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of membrane-bound and soluble receptor activator of NF-kappa B ligand (RANKL) in human T cells.2004

    • Author(s)
      Kanamaru F, Iwai H, Ikeda T, Nakajima A, Ishikawa I, Azuma M
    • Journal Title

      Immunol Lett. 94(3)

      Pages: 239-246

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Distribution of Bacteroides forsythus genotypes in a Japanese periodontitis population.2003

    • Author(s)
      Huang Y, Umeda M, Takeuchi Y, Ishizuka M, Yano-Higuchi K, Ishikawa I
    • Journal Title

      Oral Microbiol Immunol 54・5

      Pages: 648-657

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 2003 Consensus report, workshop on contemporary science in clinical periodontics.2003

    • Author(s)
      Ishikawa I et al.
    • Journal Title

      Annals of Periodontology 8・1

      Pages: 34-37

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cloning of the Tannerella forsythensis (Bacteroides forsythus) siaHI gene and purification of the sialidase enzyme.2003

    • Author(s)
      Ishikura H, Arakawa S, Nakajima T, Tsuchida N, Ishikawa I.
    • Journal Title

      J Med Microbiol 52

      Pages: 1-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prostaglandin E2 downregulates interleukin-12 production through EP4 receptors in human monocytes stimulated with lipopolysaccharide from Actinobacillus2003

    • Author(s)
      Iwasaki K, Noguchi K, Ishikawa I.
    • Journal Title

      Oral Microbiol Immunol 18

      Pages: 150-155

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Novel isolation of alkaline phosphatase-positive subpopulation from periodontal ligamentfibroblasts.2003

    • Author(s)
      Murakami Y, Kojima T, Nagasawa T, Kobayashi H, Ishikawa I.
    • Journal Title

      J Periodontol. 74・6

      Pages: 780-786

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gene expression of growth differentiation factors in the developing periodontium of rat molars.2003

    • Author(s)
      Sena K, Morotome Y, Baba O, Terashima T, Takano Y, Ishikawawa I.
    • Journal Title

      J Dent Res 82・3

      Pages: 166-171

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cloning of the Tanmerella forsythensis (Bacteroides forsythus) siaHI gene and purification of the sialidase enzyme2003

    • Author(s)
      Ishikura H, Arakawa S, Nakajima T, Tsuchida N, Ishikawa I.
    • Journal Title

      J Med Microbiol 52

      Pages: 1-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prostaglandin E2 downregulates interleukin-12 production through EP4 receptors in human monocytes stimulated with lipopolysaccharide from Actinobacillua actinomecetemcomitans2003

    • Author(s)
      Iwasaki K, Noguchi K, Ishikawa I.
    • Journal Title

      Oral Microbiol Immunol 18

      Pages: 150-155

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Novel isolation of alkaline phosphatase-positive subpopulation from periodontal ligamentfibroblasts2003

    • Author(s)
      Murakami Y, Kojima T, Nagasawa T, Kobayashi H, Ishikawa I.
    • Journal Title

      J Periodontol 74・6

      Pages: 780-786

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Up-regulation of co-stimulatory molecule expression and dendritic cell marker (CD83) on B cells in periodontal disease.2002

    • Author(s)
      Mahanonda R, Sa-Ard-Ian N, Yongvanitchit K, Wisetchang M, Ishikawa I, Nagasawa T, Waish DS
    • Journal Title

      J Periodont Res 37・3

      Pages: 177-118

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] LPS-stimulated human gingival fibroblasts inhibit the differentiation of monocytes into osteoclasts through the production of osteoprotegerin2002

    • Author(s)
      Nagasawa T, Kobayashi H, Kiji M, Aramaki M, Mahanonda R, Kojima T, Murakami Y, Saito M, Morotome Y, Ishikawa I
    • Journal Title

      Clin.Exp.Immunol. 130・2

      Pages: 338-334

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Synergistic effect of fibroblast growth factor-4 in ectopic bone formation induced by bone morphogenetic protein-2.2002

    • Author(s)
      Kubota K, Iseki S, Kuroda S, Oida S, Iimura T, Duarte WR, Ohya K, Ishikawa I, Kasugai
    • Journal Title

      Bone 31・4

      Pages: 465-447

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Enhancing effect of Tob deficiency on bone formation is specific to bone morphogenetic protein-induced osteogenesis.2002

    • Author(s)
      Usui M, Yoshida Y, Yamashita T, Tsuji K, Ishikawa I, Yamamoto T
    • Journal Title

      J Bone Miner Res 17

      Pages: 1026-1023

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Histocompatible healing of Periodontal Defects After Application of an Injectable Calcium Phosphate Bone Cement.2002

    • Author(s)
      Shirakata Y, Oda S, Kinoshita A, Kikuchi S, Tsuchioka H, Ishikawa I
    • Journal Title

      J Periodontol 73

      Pages: 1043-1045

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Three case reports of aggressive periodontitis associated with Porphyromonas gingivalis in younger patients.2002

    • Author(s)
      Ishikawa I, Kawashima Y, Oda S, Iwata T, Arakawa S.
    • Journal Title

      J Periodont Res 37

      Pages: 324-333

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Enhancing effect of Tob deficiency on bone formation is specific to bone morphogenetic protein-induced osteogenesis2002

    • Author(s)
      Usui M, Yoshida Y, Yamashita T, Tsuji K, Ishikawa I, Yamamoto T
    • Journal Title

      J Bone Miner Res 17

      Pages: 1026-1033

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] LPS-stimulated human gingival fibroblasts inhibit the differentiation of monocytes into osteoclasts through the production of osteoprotegerin

    • Author(s)
      Nagasawa T, Kobayashi H, Kiji M, Aramaki M, Mahanonda R, Kojima T, Murakami Y, Saito M, Morotome Y, Ishikawa I
    • Journal Title

      Clin.Exp.Immunol 130・2

      Pages: 338-344

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Lasers in Dentistry-Revolution of Dental Treatment in the New Millennium : Proceedings of the 8th International Congress on Lasers in Dentistry.2003

    • Author(s)
      Ishikawa I, Frame JW, Aoki A (Eds.)
    • Total Pages
      489
    • Publisher
      ElsevierScience, Amsterdam
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Huang Y, Umeda M, Takeuchi Y, Ishizuka M, Yano-Higuchi K, Ishikawa I: "Distribution of Bacteroides forsythus genotypes in a Japanese periodontitis population."Oral Microbiol Immunol. 54・5. 648-657 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishikawa I et al.: "2003 Consensus report, workshop on contemporary science in clinical periodontics."Annals of Periodontology. 8・1. 34-37 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishikura H, Arakawa S, Nakajima T, Tsuchida N, Ishikawa I.: "Cloning of the Tannerella forsythensis (Bacteroides forsythus) siaHI gene and purification of the sialidase enzyme."J Med Microbiol. 52. 1-7 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iwasaki K, Noguchi K, Ishikawa I.: "Prostaglandin E2 downregulates interleukin-12 production through EP4 receptors in human monocytes stimulated with lipopolysaccharide from Actinobacillus."Oral Microbiol Immunol. 18. 150-155 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Murakami Y, Kojima T, Nagasawa T, Kobayashi H, Ishikawa I.: "Novel isolation of alkaline phosphatase-positive subpopulation from periodontal ligamentfibroblasts."J Periodontol. 74・6. 780-786 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sena K, Morotome Y, Baba O, Terashima T, Takano Y, Ishikawawa I.: "Gene expression of growth differentiation factors in the developing periodontium of rat molars."J Dent Res. 82・3. 166-171 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishikawa I, Frame JW, Aoki A (Eds.): "Lasers in Dentistry-Revolution of Dental Treatment in the New Millennium : Proceedings of the 8th International Congress on Lasers in Dentistry"ElsevierScience, Amsterdam. 489 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mahanonda R, Sa-Ard-Ian N, Yougvanitchit K, Wisetehang M, Ishikawa I, Nagasawa T, Waish DS, Pichyangkul S: "Up-regulation of co-stimulatory molecule expression and dendritic cell marker (CD83) on B cells in periodontal discase"J Periodont Res. 37・3. 177-183 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagasawa T., Kobayashi H., Kiji M., Aramaki M., Mahanonda R., Kojima T., Murakami Y., Saito M., Morotome Y., Ishikawa I: "LPS-simulated human gingival fibroblasts inhibit the differentiation of monocytes into osteoclasts through the production of osteoprotegerin"Clin. Exp. Immunol.. 130・2. 338-344 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kubota K., Iseki S., Kuroda S., Oida S., Iimura T., Duarte WR., Ohya K., Ishikawa I., Kasugai S.: "Synergisticeffect of fibroblast growth factor-4 in ectopic bone formation induced by bone morphogenetic protein-2"Bone. 31・4. 465-471 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Usui M., Yoshida Y., Yamashita T., Tsuji K., Ishikawa I., Yamamoto T., Nifuji A.: "Enhncing effect of Tob defieiency on bone formation is specific to bone morphogenetic protein-induced osteogenesis"J Bone Miner Res. 17. 1026-1033 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shirakata Y., Oda S., Kinoshita A., Kikuchi S., Tsuchioka H., Ishikawa I.: "Histocompatible healing of Periodontal Defects After Applieation of an Injectable Caleium Phosphate Bone Cement"J Periodontol. 73. 1043-1053 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishikawa I., Kawashima Y., Oda S., Iwata T., Arakawa S.: "Three case reports of aggressive periodontitis associated with Porphyromonas gingivalis in younger patients"J Periodont Res.. 37. 324-332 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Noguchi K, Iwasaki K, Shitashige M, Umeda M, Izumi Y, Murota S, Ishikawa I.: "Downregulation of lipopolysaccharide-induced intercellular adhesion molecule-1 expression via EP2/EP4 receptors by prostaglandin E2 in human fibroblasts."Inflammation. 25. 75-81 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Noguchi K, Endo H, Kondo H, Ishikawa I.: "Prostaglandin F2alpha upregulates interleukin-6 production in human gingival fibroblasts."J Periodont Res.. 36. 80-87 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Noguchi K, Shitashige M, Endo H, Kondo H, Yotsumoto Y, Izumi Y, Nitta H, Ishikawa I.: "Involvement of cyclooxygenase-2 in serum-induced prostaglandin production by human oral gingival epithelial cells."J Periodont Res.. 36. 124-130 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Noguchi k, Tominaga Y, Matsushita K, Izumi Y, Endo H, Kondo H, Ishikawa I.: "Prostaglandin F2a upregulates matrix metalloproteinase-1 production in human gingival fibroblasts."J Periodont Res.. 36. 334-339 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sakamoto M, Takeuchi Y, Umeda M, Ishikawa I, Benno Y.: "Rapid detection and Quantification of Five Periodontopathic Bacteria by Real-Time PCR."Microbiol Immunol. 45. 39-44 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takeuchi Y, Umeda M, Sakamoto M, Benno Y, Ishikawa I.: "Treponema socranskii, Treponema denticola, and Porphyromonas gingivalis are associated with severity of periodontal tissue destruction."J Periodontol. 72. 1354-1363 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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