1998 Fiscal Year Final Research Report Summary
Role of gas mediators in degradation of articular cartilage
| Project/Area Number |
09470322
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Kinki University |
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Principal Investigator |
TANAKA Seisuke Kinki University School of Medicine, Department of Orthopaedic Surgery, Professor, 医学部, 教授 (00026840)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAGI Ichiro Kinki University, School of Medicine, Department of Orthopaedic Surgery, Instruc, 医学部・附属病院, 助手 (30288906)
OTANI Kazuhiro Kinki University School of Medicine, Department of Orthopaedic Surgery, Instruct, 医学部, 助手 (20258031)
FUKUDA Kanji Kinki University School of Medicine, Department of Orthopaedic Surgery, Lecturer, 医学部, 講師 (50201744)
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| Project Period (FY) |
1997 – 1998
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| Keywords | chondrocytes / nitric oxide / superoxide / peroxynitrite / proteoglycan |
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| Research Abstract |
Although arthrosis, such as rheumatoid arthritis, is one of the popular pathway of joint deterioration, the underlying mechanism of cartilage degradation has not been clarified.
We reported the significance of nitric oxide (NO) and superoxide (SO) in the interleukin-i (IL-1) mediated cartilage degradation. In this series of experiment, we have focused on the mechanism of IL-1-inhibited proteoglycan (PG) synthesis. SIN-1, which leads to simultaneous generation of both NO and su peroxide inhibited PG synthesis. Both superoxide dismutase and hemoglobin reversed SIN-1-inhibited PG synthesis, indicating the simultaneous generation of superoxide is essential to inhibit PG synthesis. IL-1 induced peroxynitrite in articular chondrocytes and addition of peroxynitrite resulted in inhibiting PG synthesis, thereby suggesting that the concurrent generation of superoxide anion and NO is required for the action of IL-1 to inhibit PG synthesis. Peroxynitrite is a candidate for this underlying mechanism.
To examine the role of gas mediator in vivo, transplantation of cartilage was carried out. We made full thickness cartilage defect in the rabbit knee joint (defect model). When perichondrium was transplanted in the defect, degradation of surrounding articular cartilage was inhibited (repair model). The levels of superoxide and NO in the surrounding cartilage of the defect model were significantly higher than the repair model.
These data suggest that gas mediator plays an important role in the cartilage degradation.
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