1993 Fiscal Year Final Research Report Summary
Mechanism of cartilage degradation in rheumatoid arthritis
| Project/Area Number |
04670892
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Kobe University |
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Principal Investigator |
MATUBARA Tsukasa Kobe University Hospital, Assistant professor, 医学部・附属病院, 講師 (80192342)
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| Co-Investigator(Kenkyū-buntansha) |
SAEGUSA Yasuhiro Kobe University of Medicine, assistant, 医学部, 助手 (30215579)
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| Project Period (FY) |
1992 – 1993
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| Keywords | polymorphonuclear leukocyte / chondrocyte cytotoxity / hydorigen peroxide / cholesterol epoxide / cartilage deradation / rheumatoid arthritis / コレステロールエポキサイド |
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| Research Abstract |
In order to study the mechanism of cartilage degradation, we have studied, in this investigation, the chondrocyte damage by activated polymorphonuclear leukocytes(PMNLs). The cultured chondrocytes were pre-labeled by ^<51>Cr, and then co-cultured by PMNLs in the presence of phorbol ester or heat-aggregated IgG.The activated PMNLs promoted ^<51>Cr release from the chondrocytes. The PMNL-induced chondrocyte cytotoxicity was abolished by addition of catalase in the culture. These results suggest that hydrogen peroxide generated by activated PMNLs are responsible for the observed chondrocyte cytotoxicity. To further study the mechanism of hydrogen peroxide-induced chondrocyte cytotoxicity, the chondrocytes were cultured in the presence of hydrogen peroxide and the oxidation of chondrocyte lipid was analyzed. Hydrogen peroxide increased the generation of cholesterol epoxide in the cultured chondrocytes as well as chondrocyte cytotoxicity in a dose-dependent fashin. Cholesterol epoxide, exogenously added to the chondrocyte culture, also promoted chondrocyte cytotoxicity. It is, therfore, suggested that the chondrocyte lipid oxidationn by PMNL-derived hydrogen peroxide is critical in the induction of chondrocyte damage by PMNLs, and , in this way, plays an essential role in cartilage degradation in inflammatory process.
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