2003 Fiscal Year Final Research Report Summary
The expression of m-calpain in human synovial fibroblasts and chondrocytes.
| Project/Area Number |
14571368
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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 | Gifu University School of Medicine |
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Principal Investigator |
ITOH Yoshiki Gifu University School of Medicine, Dept. of Orthopaedic Surgery, Assistant, 医学部附属病院, 助手 (10313884)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Katsuji Gifu University School of Medicine, Dept. of Orthopaedic Surgery, Professor, 医学部, 教授 (90170969)
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| Project Period (FY) |
2002 – 2003
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| Keywords | calpain / chondrocyte / NSAIDs / TNF-α / arthritis |
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| Research Abstract |
Calpain is generally believed to function only in the cytoplasm. However, m-calpain has recently been detected in the extracellular spaces of arthritic joint tissues. We attempted to examine the expression and secretion of m-calpain in a human chondrocytic cell line, HCS2/8 stimulated by TNF-α Cells were stimulated by TNF-α, and the expression of m-calpian in the cells and culture medium was analyzed by Western blotting. The effects of NSAIDs on the expression of m-calpain were also examined.
TNF-α increased the level of m-calpain in the culture medium in a dose-and time-dependent manner.Intracellular m-calpain increased at 24 h and thereafter gradually to decreased to 48 h. NSAIDs, aspirin, diclofenac sodium, loxoprofen-SRS and NS398 significantly inhibited TNF-α-induced increase of m-calpain in the medium and cells. Prostaglandin E_2 stimulated the effect of low concentrations of TNF-α on m-calpain expression. In contrast, prostanoid-receptor antagonists inhibited the effects of TNF-α.
Increase of m-calpain in the culture medium suggests that this Ca^<2+>-dependent protease may play a role in the promotion of degradation of cartilage extra-cellular matrix during arthritis. NSAIDs have protective effects, at least in part, through the inhibition of the expression and secretion of m-calpain.
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