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Angiogenic action of gliostatin in rheumatoid arthritis and its molecular mechanism

Research Project

Project/Area Number 16591504
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionNAGOYA CITY UNIVERSITY

Principal Investigator

NAGAYA Yuko  Nagoya City University, Graduate School of Medical Sciences, Research Associate, 大学院・医学研究科, 助手 (90291583)

Co-Investigator(Kenkyū-buntansha) OTSUKA Takanobu  Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学研究科, 教授 (10185316)
ASAI Kiyohumi  Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学研究科, 教授 (70212462)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsrheumatoid arthritis / synoviocytes / angiogenesis / gliostatin / VEGF / DNA microarray system / gene transfection
Research Abstract

Neovascularization, proliferation of synovial cells, and mononuclear cell influx and activation are characteristic events observed in synovial joints in the pathohistology of rheumatoid arthritis (RA). We have previously measured the concentration of the angiogenic factor, gliostatin (GLS), in sera and synovial fluids of RA patients, and demonstrated for the first time an enormously high concentration in RA synovial fluids as well as in RA sera. Furthermore our previous study demonstrated that GLS acts as a cytokine to augment its own synthesis in fibroblast-like synoviocytes (FLSs) obtained from patients with RA through an autocrine mechanism. It should be noted that GLS additionally caused induction and extracellular secretion of matrix metalloproteinase (MMP)-1 and MMP-3 triggering cartilage degeneration. Recently we reported that intraarticular injection of rHuGLS to rabbit knees induced RA-like synovitis.
The purpose of this study was to elucidate whether GLS/TP is involved in the regulation of the angiogenic cytokine vascular endothelial growth factor (VEGF) in rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLSs) from patients with RA were cultured and stimulated with recombinant human GLS (rHuGLS) and interleukin (IL)-1β. Immunohistochemistry showed that GLS/TP and VEGF were detectable in the synovial lining cells. In cultured FLSs, both VEGF mRNA and protein levels were markedly increased by rHuIL-1βtreatment. rHuGLS increased VEGF mRNA expression in a dose-dependent manner. We detected high concentrations of VEGF165 protein in culture supernatants from FLSs treated with rHuGLS (300ng/ml), which were comparable to GLS levels found in synovial fluid of RA patients. These findings indicate that GLS/TP and VEGF have synergistic effects on angiogenesis in rheumatoid synovitis, and that GLS/TP has a role in regulating VEGF.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (4 results)

All 2005 2004

All Journal Article (4 results)

  • [Journal Article] The inhibitory effect of disease-modifying anti-rheumatic drugs and steroids or gliostatin/platelet-derived endothelial cell growth factor production in human fibroblast like synoviocytes.2005

    • Author(s)
      Kusabe Takuma, et al.
    • Journal Title

      Rheumatology International 25

      Pages: 625-630

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The inhibitory effect of desease-modifying anti-rheumatic drugs and steroids on gliostatin/platelet-derived endothelial cell growth factor production in human fibroblast-like synoviocytes.2005

    • Author(s)
      Kusabe Takuma, et al.
    • Journal Title

      Rheumatology International 25

      Pages: 625-630

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The inhibitory effect of disease-modifying anti-rheumatic drugs and steroids on gliostatin/platelet-derived endothelial cell growth factor production in human fibroblast-like synoviocytes.2005

    • Author(s)
      Kusabe Takuma
    • Journal Title

      Rheumatology International 25

      Pages: 625-630

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Neuropathic arthropathy caused by chondrosarcoma of the cervical spine. A case report.2004

    • Author(s)
      Waguri-Nagaya Y, Otsuka T, et al.
    • Journal Title

      Mod Rheumatol 14

      Pages: 160-163

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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