| Project/Area Number |
10470309
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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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 |
MATSUI Nobuo Nagoya City University, Medical School, Professor, 医学部, 教授 (40009569)
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| Co-Investigator(Kenkyū-buntansha) |
ASAI Kiyofumi Nagoya City University, Medical School, Associate Professor, 医学部, 助教授 (70212462)
NAGAYA Yuko Nagoya City University, Medical School, Research Associate, 医学部, 助手 (90291583)
OTSUKA Takanobu Nagoya City University, Medical School, Assistant professor, 医学部, 講師 (10185316)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1998: ¥7,300,000 (Direct Cost: ¥7,300,000)
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| Keywords | gliostatin / platelet-derived endothelial cell growth factor / thymidine phosphorylase / rheumatoid arthritis / synoviocytes / rabbit / matrix metalloproteinases |
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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). The purposes of this study are to examine how gliostatin/platelet derived-endothelial cell growth factor (GLS/PD-ECGF) is involved in the molecular mechanism of cartilage degradation in RA with special reference to the GLS-induced gene expression and protein synthesis of matrix metalloproteinase (MMP)-1 (collagenase-1) and MMP-3 (stromelysin-1) and to examine synovial inflammation in rabbit knees induced by intraarticular administration of human GLS/PD-ECGF.
GLS demonstrated a self induction of mRNA in cultured RA synoviocytes. GLS evoked a dose-dependent induction of MMP-1 and MMP-3 mRNAs and subsequently their extracellular secretions. Intraarticular injection of rHuGLS resulted in development of diffuse synovitis resembling rheumatoid arthritis. The mutant protein which was prepared by site-directed mutagenesis and lacking dThdPase activity also brought out the same effect.
These findings suggest that GLS is a plausible pathogenic factor causing the extensive joint destruction in RA mediated via MMPs and that human GLS can cause RA-like synovitis in rabbit knee joints via a mechanism other than its thymidine phosphorylase activity.
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