2007 Fiscal Year Final Research Report Summary
Therapeutic research for osteoporosis with rheumatoid arthritis
| Project/Area Number |
18591129
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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 (80333243)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Yoshiya University of Occupational&Environmental Health, School of Medicine, Professor (30248562)
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| Project Period (FY) |
2006 – 2007
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| Keywords | RA synovial endothelial cells / M-CSF / RANKL / Osteoblast / Osteoclast |
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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 RA endothelial cells (RAECs) 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. Specifically, up-regulated gene in RAECs was 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 RAECs. Genes of fibroblast growth factor-2, interleukin-6 and osteoprotegerin were also overexpressed on RAECs. 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 RAECs is involved in osteoclastogenesis from monocytes, migration and TRAP-positive MNC formation.
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