Arthritogenic action of gliostatin in rheumatoid arthritis and its molecular mechanism.
| Project/Area Number |
13671529
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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, Graduate School of Medical Sciences |
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Principal Investigator |
OTSUKA Takanobu Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学研究科, 教授 (10185316)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAYA Yuko Nagoya City University, Graduate School of Medical Sciences, Research Associate, 大学院・医学研究科, 助手 (90291583)
松井 宣夫 名古屋市立大学, 医学部, 教授 (40009569)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | gliostatin / platelet-derived endothelial cell growth factor / thymidine phosphorylase / rheumatoid arthritis / synoviocytes / rabbit / matrix metalloproteinases / arthroplasty / 関節内注射 / 滑膜切除術 / Matrix metallopoteinases |
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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 and whether measurement of serum GLS can be used to evaluate symptomatic improvements after surgery (arthroplasty or synovectomy) in RA.
Intraarticular injection of rHuGLS in rabbit knee joints resulted in development of diffuse synovitis, chondrocytes destruction, and pannus formation resembling rheumatoid arthritis. A chondrosarcoma cell line (OUMS-27) was cultured and treated with interleukin-lβ (IL-1β). IL-1β induced the expression of matrix metalloproteinase (MMP)-1, MMP-13, and GLS. Patients with RA undergoing arthroplasty demonstrated a decrease in serum GLS levels after operations.
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 via a mechanism other than its thymidine phosphorylase activity and that the serum GLS level is a useful indicator for evaluation of synovitis and the systemic efficacy of surgical treatment.
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Report
(3 results)
Research Products
(15 results)
