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The role of adhesion molecules of osbeoblasts andosteoclasts in bone destruction of rheumatoid arthristis patients

Research Project

Project/Area Number 05670425
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 内科学一般
Research InstitutionKYUSHU UNIVERSIT

Principal Investigator

SINGU Masao  Kyushu University Medical Institute of Bioregulation Associate Professor, 生体防御医学研究所, 助教授 (10038523)

Co-Investigator(Kenkyū-buntansha) EZAKI Ichiko  Kyushu University Medical Institute of Bioregulatio Lecturer, 生体防御医学研究所, 助手 (40037453)
末永 康夫  九州大学, 生体防御医学研究所, 助手 (20264111)
和田 哲也  九州大学, 生体防御医学研究所, 助手 (30220958)
野中 史郎  九州大学, 生体防御医学研究所, 助手 (60198603)
橋本 通  九州大学, 生体防御医学研究所, 助手 (00237950)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
KeywordsRheumatoid arthristis / Osteoclast / Osteoblast / Adhesion molecule / ICAM-1 / Type I collagen fragment / ICAM-1単クローン抗体 / IL-1β / IL-1beta
Research Abstract

The adhesion molecules such as ICAM-1, VCAM-1, ELAM-1 and ICAVM-1, LA-4 in human osteoblasts(OB) and osteoclastic cells(OC), respectively, obtained from rhheumatoid arthristis(RA)patients were expressed and enhanced by inflammatory cytokines.OB/OC interaction mediated by such adhesion molecules induced the suppression of osteoplastic properties of OB,leading to bone destruction and bone resorption. The bone destruction was mediated by metalloproteases, cytokines and oxygen free radicals produced by OC.There were no differences of bone resorbin activity between RA OC and osteoarthristis OC.Some synovial cells obatained from RA showed bone resorbing activity. The measurement of type I collagen fragment by specifice ELISA well reflected bone resoprtion, and more sensitive than pit assay. OC or OB cultured with antiICAM-l monoclonal antibody(mab)showed enhanced expression of VCAM-1 and ELAM-1, suggesting that there are some adhesion molecule cascades like in endothelial cells. Accordingly, ICAM-1 mab did not suppress arthristis in CII-mediated artghritis in mice. OC from RA patients showed increased bone resobing activity, where as frequency of TRAP staining was not increased.

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (48 results)

All Other

All Publications (48 results)

  • [Publications] Shingu, M.: "Induction of severe forms of synovitis and subsequent destruction of cartilage and bone in type II collagen (CII) arthritis (CA) in IL-6 transgenic mice (IL-6TRM)." Arthritis Rheum. 38. s234 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tsuruta, H.: "Quantitation of IL-1β mRNA by a combined method of RT-PCR and on ELISA based on ion-sensitive field effect transistor." J Immunol Method. 180. 259-264 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Fujikawa, Y.: "interleukin I receptor antagonist production in cultured synovial cells from patients with rheumatoid arthritis and osteoarthritis." Ann Rheum Dis. 54. 318-320 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shingu, M.: "The role of IL-4 and IL-6 in IL-1-dependent Cartilage Matrix Degradation." Brit J Rheumatol. 34. 101-106 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kuroki, T.: "Effects of cytokines on alkaline phosphatase and osteocalcin priduction, calcification and calcium release by human osteoblastic cells." Brit J Rheumatol. 33. 224-230 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shingu, M.: "Increased IL-1 receptor antagonist (IL-1ra) production and decreased IL-1-β/IL-1ra ratio in mononuclear cells from rhematoid arthritis patients." Brit J Rheumatol. 34. 24-30 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shigu.M., Okada, M., Ezaki, I., et al.: "Induction of severe forms of synovitis and subsequent destruction of cartilage and bone in type II collagen(CII)arthritis(CA) in IL-6 transgenic mice(IL-6TRM)." Arthritis Rheum. 38. s324 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tsuruta, H., Matsui, S., Oka, K., Namba, T., Shingu, M., et al.: "Quantitation of IL-1beta mRNA by a combined method of RT-PCR and an ELISA based on ion-sensitive field effect transistor" J Immunol Method. 180. 259-264 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Fujikawa, Y., Shingu, M., Torisu, T., et al: "Interleukin 1 receptor antagonist production in cultured synovial cells from patients with rheumatoid arthristis and osteoarthritis." Ann Rheum Dis. 54. 318-320 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shingu, M., Miyauchi, S., Nagai, Y., et al: "The role of IL-4 and IL-6 in ILL-1-dependent Cartilage Matrix Degradation." Brit J Rheumatol. 34. 101-106 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kuroki, T., Shingu, M., Koshihara, Y., et al.: "Effects of cytokines on alkaline phosphatase and osteocalcin production, calcification and calcium release by human osteoblastic" cells. Brit J Rheumatol. 33. 224-230 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shingu, M., Fujikawa, Y., Waka, T., et al: "Increased IL-1 receptor antagonist(IL-1ra)production and decreased IL-1ra ratio in mononuclear cells from rheumatoid arthritis patients" Brit J Rheumatol. 34. 24-30 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shingu,M.: "Induction of severe forms of synovitis and subsequent destruction of cartilage and bone in type II collagen(CII) arthritis(CA) in IL-6 transgenic mice(IL-6TRM)." Arthritis Rheum. 38. s234 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tsuruta,H.: "Quantitation of IL-1β mRNA by a combined method of RT-PCR and an ELISA based on ion-sensitive field effect transistor." J Immunol Method. 180. 259-264 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fufikawa,Y.: "Interleukin 1 receptor antagonist production in cultured synovial cells from patients with rheumatoid arthritis and osteoarthritis." Ann Rheum Dis. 54. 318-320 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shingu,M,: "The role of IL-4 and IL-6 in IL-1-dependent Cartilage Matrix Degradation." Brit J Rheumatol. 34. 101 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kuroki,T.: "Effects of cytokines on alkaline phosphatase and osteocalcin production, calcification and calcium release by human osteoblastic cells." Brit J Rheumatol. 33. 224-230 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shingu,M.: "Increased IL-1 receptor antagonist(IL-1ra) production and decreased IL-1β/IL-1ra ratio in mononuclear cell from rheumatoid arthritis patients." Brit J Rheumatol. 34. 24-30 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kuroki.T.: "Effects of cytokines on alkaline phosphatase and osteocalcin production,calcification and calcium release by human osteoblastic cells." British J Rheumatol. 33. 224-230 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 神宮政男.: "オ-ラノフィンの慢性関節リウマチ患者単核球リウマトイド因子およびサイトカイン産生抑制作用." 炎症. 14. 21-23 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nobunaga,M.: "Course and outcome of rheumatoid arthritis:Comparisons among the patients in these 40 years." Jpn.J.Rheumatol.(in press). (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shingu,M.: "Complement degradation products in rheumatoid arthritis synovial fluid." British J Rheumatol. 33. 299-300 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shingu,M.: "Production of soluble ICAM‐1 by mononuclear cells from patients with rheumatoid arthritis." Inflammation. 18. 23-32 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shingu,M.: "Possible mechanism of vascular in pre‐eclampsia in damage pre‐eclampsia." J.Human Hypertension. 8. 177-180 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 神宮政男,: "骨芽細胞と破骨細胞における接着分子発現と細胞間相互作用-慢性関節リウマチの骨破壊における関与-" 炎症. 14. 467-472 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shingu,M.: "Anti‐inflammatory effects of recombinant human manganese superoxide dismutase on adjuvant arthritis in rats." Rheumatol Int. 14. 77-81 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shingu,M.: "Role of oxygen radicals and IL‐6 in IL‐1‐dependent cartilage matrix degradation." Inflammation. 18. 413-423 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shingu,M.: "Effects of cytokine‐induced soluble ICAM‐1 from human synovial cells on synovial cell‐lymphocyte adhesion." Clin Exp Immunol. 97. 46-51 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 神宮政男,: "慢性関節リウマチ患者単核球によるsoluble IL‐2 receptor,IL‐4およびIL‐6産生に対するオ-ラノフィンの影響." 炎症. 14. 401-404 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 任 〓雪,: "膠原病患者におけるInterleukin‐1 receptor antagonistの意義." リウマチ科. 11. 260-261 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ezaki.I.: "Analysis of the genes encoding yhe variable regions if human IgG rheumatoid factor." J.Rheumatol. 21. 2005-2010 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hashimoto.H.: "Production of soluble ICAM‐1 from human endothelial cells by IL-1β and THF‐α." Inflammation. 18(2). 163-173 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 橋本 通,: "慢性関節リウマチ患者血清中エリスロポイエチン・G‐CSF濃度に関する検討" リウマチ科. 12(3). 219-223 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 橋本 通,: "慢性関節リウマチに皮膚筋炎を合併した2症例." 内科. 74(5). 975-977 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 橋本 通,: "成人/小児発症Still病に続発した消化管アミロイドーシスの3症例." 臨床リウマチ. 6(2). 93-101 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 橋本 通,: "皮膚筋炎を合併した慢性関節リウマチ症例‐とくに酵素結合免疫グロブリンについて." 九州リウマチ. 14(2)(in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 橋本 通,: "若年性関節リウマチ,慢性関節リウマチに続発した小腸アミロイドーシスの2例." リウマチ. 35(1)(in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 神宮政男,: "慢性関節リウマチ患者末梢血単核球によるsoluble IL‐2 receptor,IL‐4およびIL‐6産生に対するオ-ラノフィンの抑制作用" 炎症. 14. 401-404 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 神宮政男,: "慢性関節リウマチ患者単核球に対するT‐614およびその誘導体の影響" 炎症. 15. 55-59 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 神宮政男,: "早期慢性関節リウマチ診断における血清MMP‐3濃度測定の臨床的意義" リウマチ. 35. 15-24 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kuroki.T.: "Effects of cytokines on Alkaline Phosphatase and osteocalcin production,calcification and calcium release by human osteoblastic cells." British J Rheumatol. 33. 224-230 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shingu,M.: "The role of LI‐4 and IL‐6 in IL‐1‐Dependent cartilage matrix degradation" British J Rheumatol. 34(in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 神宮政男,: "専門医による慢性関節リウマチの治療指針." メディカルレビュー社,大阪., (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Masao Shingu: "The effects of cytokines on metalloproteinase inhibitors and collagenase produc-tion by human chondrocytes and TIMP production by synovial cells induced by IL-1B" Clin Exp Immunol. 94. 145-149 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masao Shingu: "Production of soluble ICAM-1 by mononuclear cells from patients with rheumatoid arthritis" Inflammation. 18. 23-32 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masao Shingu: "The effects of intercellualr adhesion molecule-1 monoclonal antibody(MAB) on the expression of adhesion molecules in synovial cells(SC)." Arthritis Rheum. 36(Suppl). s155-s155 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tatefumi Kuroki: "Effects of cytokines on alkaline phosphatase and osteocalcin production,calcif-ication and calcium release by human osteoblastic cells." Brit J Rheumatol. 33. 224-230 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Michi Hashimoto: "Production of soluble ICAM-1 from human endothelial cells induced by IL-1beta and TNF-alpha" Inflammation. 18. 163-173 (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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