| Project/Area Number |
13671547
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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 | St. Marianna University School of Medicine |
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Principal Investigator |
NAKAMURA Hiroshi St. Marianna University School of Medicine, Institute of Medical Science, associated professor, 難病治療研究センター, 講師 (80227933)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Tomohiro St. Marianna University School of Medicine, Institute of Medical Science, assistant professor, 難病治療研究センター, 助教授 (80233807)
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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 |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | osteoarthritis / Immune response / inflammation / animal model / YKL-39 / cartilage intermediate layer protein (CLIP) / pannus / CILP / 関節炎 |
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| Research Abstract |
Osteoarthritis (OA) is frequent during aged population and is caused by damage of articular cartilage. As far, :aging or mechanical stress have been considered to be a cause of articular change, however recent studies show that inflammatory mediators have an important role in the articular degradation. As a result of our previous study (project No. 11671461), we showed that T cells infiltrated into synovial tissue from patients with OA and autoantibodies against osteopontin, YKL-39 and intermediate layer protein (CILP) were present in sera of the patients. In this term, the immune mechanism in osteoarthritis (OA) was investigated further and following results were obtained.
1. The presence of inflammatory reactions : C5aR, one of compliment receptors was expressed in OA chondrocytes. Chemokines such as MCP-1, MIP-1 and RANTES are secreted from articular chondrocytes and their receptors (CCR2 and CCR5) were expressed in chondrocytes. Among these, RANTES and MCP-1 had catabolic effects on articular cartilage enhancing MMP production and suppressing proteoglycan synthesis from chondrocytes.
1. Arthritogenicity of YKL-39 and CILP : Immunization of YKL-39 and CILP induced chronic and oligo-arthritis in some mouse strains. Moreover, responsible epitopes were investigated. Histrologically, synovitis and articular involvement were shown and ectopic ossification was found following CILP immunization.
1. The presence of pannus-like tissue : Pannus-like soft tissue was frequently found on the surface of OA cartilage and the tissue had catabolic characteristics expressing IL-1 and MMP-3.
1. Interaction of chondrocytes with T cells : Direct contact of chondrocytes with autologous T cells enhanced MMP and RANTES production leading further articular degradation.
1. Future plan : Transfer of immune cells from OA model animals to normal subjects are investigated at present.
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