Abstract
Aggrecanases are considered to play a key role in the destruction of articular cartilage during the progression of arthritis. Here we report that the N-terminal inhibitory domain of tissue inhibitor of metalloproteinases 3 (N-TIMP-3), but not TIMP-1 or TIMP-2, inhibits glycosaminoglycan release from bovine nasal and porcine articular cartilage explants stimulated with interleukin-1alpha or retinoic acid in a dose-dependent manner. This inhibition is due to the blocking of aggrecanase activity induced by the catabolic factors. Little apoptosis of primary porcine chondrocytes is observed at an effective concentration of N-TIMP-3. These results suggest that TIMP-3 may be a candidate agent for use against cartilage degradation.
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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Aggrecans
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Animals
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Apoptosis / drug effects
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Cartilage, Articular / drug effects*
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Cartilage, Articular / metabolism
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Cattle
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Cell Line
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Chondrocytes / cytology
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Chondrocytes / drug effects
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Culture Techniques
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Endopeptidases / metabolism*
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Extracellular Matrix Proteins*
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Glycosaminoglycans / metabolism*
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Humans
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Interleukin-1 / antagonists & inhibitors*
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Interleukin-1 / pharmacology
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Lectins, C-Type
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Protease Inhibitors / pharmacology
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Protein Structure, Tertiary
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Proteoglycans / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / pharmacology
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Swine
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Tissue Inhibitor of Metalloproteinase-3 / chemistry
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Tissue Inhibitor of Metalloproteinase-3 / genetics
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Tissue Inhibitor of Metalloproteinase-3 / pharmacology*
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Tretinoin / antagonists & inhibitors*
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Tretinoin / pharmacology
Substances
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Aggrecans
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Extracellular Matrix Proteins
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Glycosaminoglycans
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Interleukin-1
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Lectins, C-Type
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Protease Inhibitors
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Proteoglycans
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Recombinant Proteins
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Tissue Inhibitor of Metalloproteinase-3
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Tretinoin
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Endopeptidases
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aggrecanase