Abstract
Extracts of human articular cartilage have been examined for the presence of metalloproteinases that degrade proteoglycans and collagen of the extracellular matrix. Two enzymes (stromelysin and acid metalloproteinase) that degrade proteoglycan are elevated at least 150% in osteoarthritis (OA), whereas the tissue inhibitor of metalloproteinases (TIMP) shows only a small increase. We postulate an imbalance of enzyme over inhibitor that leads to net matrix destruction in OA. Stromelysin is shown to have an acid pH optimum of about 5.5. At this pH it can become spontaneously active and is less susceptible to TIMP inhibition than at pH 7.5. We postulate that the chondrocytes may secrete acid into the pericellular space, leading to localized enzyme activation and proteoglycan digestion.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cartilage, Articular / metabolism
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Cartilage, Articular / pathology
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Cartilage, Articular / physiopathology
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Collagen / metabolism
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Extracellular Matrix / metabolism
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Glycoproteins / metabolism
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Glycoproteins / physiology
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Humans
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Hydrogen-Ion Concentration
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Matrix Metalloproteinase 3
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Metalloendopeptidases / metabolism
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Metalloendopeptidases / physiology*
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Microbial Collagenase / antagonists & inhibitors
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Osteoarthritis / metabolism
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Osteoarthritis / pathology
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Osteoarthritis / physiopathology*
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Proteoglycans / metabolism
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Tissue Inhibitor of Metalloproteinases
Substances
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Glycoproteins
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Proteoglycans
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Tissue Inhibitor of Metalloproteinases
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Collagen
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Metalloendopeptidases
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Matrix Metalloproteinase 3
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Microbial Collagenase