| Project/Area Number |
11671463
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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 | Hyogo College of Medicine |
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Principal Investigator |
FUTANI Hiroyuki Hyogo College of Medicine, Research Associate, 医学部, 助手 (30248140)
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| Co-Investigator(Kenkyū-buntansha) |
MARUO Soji Hyogo College of Medicine, Professor, 医学部, 教授 (70068451)
NAKANISHI Kenji Hyogo College of Medicine, Professor, 医学部, 教授 (60172350)
MATSUI Kiyoshi Hyogo College of Medicine, Research Associate, 医学部, 助手 (00291815)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | IL-18 / IL-12 / osteoclast / metastasis / bone / osteoarthritis / rheumatoid arthritis / cancer / IL-18受容体 / 骨芽細胞 / 癌腫 |
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| Research Abstract |
1. The role of Interleukin (IL)-18 in bone resorption due to metastatic cancer :
(1) Expression of IL-18 receptor in osteoblast and osteoclast : IL-18 receptor was detected in both osteoblast and osteoclast by immunohistochemical technique. The presence of mRNAs for IL-18 receptor components was also expressed by reverse transcriptase polymerase chain reaction in these cells.
(2) The role of IL-18 in osteoclastic bone resporption in vitro condition : Osteoclastic bone resorption, purified from mice, was inhibited in co-culture with IL-18.
(3) The role of IL-18 in osteoclastic bone resporption in vivo condition : The model of bone metastasis was established by an intracardiac injection of human breast cancer cells (MDA-231) and myeloma cell (ARH-77) in nude mice. IL-18 inhibited osteolytic growth of the cancer at bone metastatic sites.
(4) The mechanism of the suppression of bone destruction by IL-18 : This activity could be synergistically enhanced by IL-12 followed by interferon gamma (IFN-γ) production.
2. The role of IL-18 in pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA).
(1) The role of IL-18 in cartilage degradation of OA : There was a relatively strong correlation of IL-18 to prostaglandin (PG)E^2 in the synovial fluid of OA.IL-18 plays an important role in the pathogenesis of OA through the PGE^2 release.
(2) Production of IL-18 in RA : IL-18 has been reported as a proinflammatory cytokine in rheumatoid arthritis (RA). We determined the IL-18 release in CD14+ macrophages by stimulation of soluble Fas ligand.
In conclusion, targeting the IL-18 appears to be an important therapeutic approach to prevent bone destruction and articular cartilage degradation, in diseases such as metastatic bone tumor, OA, and RA.
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