| Project/Area Number |
15591074
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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 |
膠原病・アレルギー・感染症内科学
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
OKADA Yosuke University of Occupational and Environmental Health, Japan, School of Medicine, Assistant Professor, 医学部, 講師 (80333243)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Yoshiya University of Occupational and Environmental Health, Japan, School of Medicine, Professor, 医学部, 教授 (30248562)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | M-CSF / rheumatoid arthritis / osteoblasts / osteoclasts / bone resorption / endothelial cells / RANKL / Gene chip / FGF-2 / ヘパラン硫酸プロテオグリカン / ICAM-1 / β_1インテグリン / 骨粗鬆症 |
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| Research Abstract |
Objective. Periarticular osteoporosis and joint destruction are major complications in rheumatoid arthritis (RA), caused by osteoclast-mediated bone resorption. However, the mechanisms of monocyte osteoclast maturation and role of rheumatoid arthritis endothelial cells (RAEC) in the control of osteoclastogenesis remain unclear. The present study was designed to determine the most important factors that influence monocyte accumulation and osteoclast formation among the many factors produced by RAEC.
Methods. We analyzed the expression profiles of various genes in human endothelial cells from various organs (RA synovium, umbilical vein, skin, liver sinusoid, renal glomerulus and brain) using oligonucleotide microarrays. The microarray data were assessed by real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and immunostaining of RA synovia. Migration of monocytes was assessed by the chemotactic chamber EZ-TAXIScanTM. Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell formation was observed by microscopy.
Results. Among many epithelial-expressed factors, macrophage-colony stimulating factor (M-CSF) gene was abundantly expressed specifically in RAEC. Fibroblast growth factor-2 (FGF-2) gene was also overexpressed on RAEC. Migration of monocytes and osteoclast formation in co-cultures promoted by culture supernatants of RAEC were inhibited by M-CSF neutralizing antibody.
Conclusion. M-CSF produced by RAEC is involved in osteoclastogenesis from monocytes ; migration, and TRAP-positive multi-nuclear cell formation, resulting in joint destruction of RA.
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