Significance of serine proteinase and matrix metalloproteinase systems in the destruction of human articular cartilage.
1. During the destruction of articular cartilage, fibrinolytic enzymes and matrix metalloproteinases (MMP) may contribute to the related pathology. The activities, antigens and messenger RNA (mRNA) levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in articular cartilage were measured in patients with no history of joint diseases (control), those with osteoarthritis (OA) classified into osteophyte-formed site (OS) and weight-bearing site (WS), and in patients with rheumatoid arthritis (RA). 2. The uPA content was higher in WS and RA compared to normal. The PAI-1 content was higher in OS and RA compared to normal. Weight-bearing site patients expressed a high uPA mRNA level but a low PAI-1 mRNA level. Osteophyte-formed site patients expressed a low uPA mRNA level but a high PAI-1 mRNA level. 3. The levels of the MMP and mRNA of tissue inhibitors of metalloproteinases (TIMP) were measured in WS, OS, and RA. In WS, the levels of MMP were high and levels of TIMP mRNA expression low. In OS, the levels of TIMP were high and levels of MMP mRNA were low. In RA, the levels of MMP and TIMP mRNA were high. 4. These findings suggest that regulation of fibrinolysis may play an important role in the matrix of articular cartilage with arthropathy.
Department of Orthopaedic Surgery, Kinki University, School of Medicine, Osakasayama, Japan.
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H
Kikuchi
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Shimada
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T
Nonaka
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Ueshima
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S
Tanaka
D000368:Aged; D000941:Antigens / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000209:etiology; D002358:Cartilage, Articular / Q000201:enzymology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000201:enzymology / Q000209:etiology; D017395:Plasminogen Activator Inhibitor 1 / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases; D014568:Urokinase-Type Plasminogen Activator / Q000276:immunology / Q000378:metabolism
D000941:Antigens; D006023:Glycoproteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D012697:Serine Endopeptidases; D014568:Urokinase-Type Plasminogen Activator; D008666:Metalloendopeptidases