Abstract
Chondrocyte metalloproteinases appear to play a major role in the development of osteoarthritis. The intracellular post-traductional mechanisms regulating collagenase and proteoglycanase are not known. Calmodulin antagonists including phenothiazine and sulfonamide derivatives significantly increased proteoglycanase activity and decreased collagenase activity. H-7, a specific inhibitor of protein kinase C, had no effect on the two metalloproteinase activities, and calmodulin was ineffective in in vitro assays upon metalloproteinase activities. We postulate that collagenase and proteoglycanase activities are controlled by calmodulin-dependent regulation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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Calmodulin / antagonists & inhibitors
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Calmodulin / physiology*
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Cartilage, Articular / enzymology*
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Humans
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In Vitro Techniques
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Isoquinolines / pharmacology
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Kinetics
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Microbial Collagenase / metabolism*
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Middle Aged
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Osteoarthritis / enzymology*
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Piperazines / pharmacology
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Protein Kinase C / antagonists & inhibitors
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Sulfonamides / pharmacology
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Trifluoperazine / pharmacology
Substances
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Calmodulin
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Isoquinolines
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Piperazines
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Sulfonamides
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Trifluoperazine
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N-(6-aminohexyl)-1-naphthalenesulfonamide
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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Protein Kinase C
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Microbial Collagenase