| Project/Area Number |
16591504
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | NAGOYA CITY UNIVERSITY |
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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)
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| 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)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| 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)
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| Keywords | rheumatoid arthritis / synoviocytes / angiogenesis / gliostatin / VEGF / DNA microarray system / gene transfection |
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| 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.
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