The effect of naproxen and interleukin-1 on proteoglycan catabolism and on neutral metalloproteinase activity in normal articular cartilage in vitro.
The events in inflammatory and degenerative joint diseases involve major changes in the metabolic events in the articular cartilage. The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on articular cartilage metabolism remain unclear, however. The objective of this catabolism of proteoglycans in articular cartilage explants maintained in culture. Release of proteoglycan from the cartilage was compared with release of neutral metalloproteinase activity. The effect of the drug also was determined on the IL-1-stimulated release of proteoglycan and neutral metalloproteinase activity from the explants. At concentrations that included those present in synovial fluids of patients treated with the drug, naproxen sodium was found to suppress the release of proteoglycan and neutral metalloproteinase activity from the articular cartilage extracts. This is in contrast to the well-documented effect of interleukin-1 (IL-1), which was shown to stimulate release of proteoglycan and neutral metalloproteinase activity from articular cartilage. The effect of naproxen sodium on the IL-1-stimulated release was to suppress, but not totally overcome, the increased release of proteoglycan and neutral metalloproteinase activity. In summary, these in vitro studies of cartilage metabolism indicate that naproxen sodium has the potential to suppress catabolic activities in articular cartilage, including those that are motivated by IL-1.
Glazer
P A
PA
Department of Orthopaedic Surgery, Columbia University, New York, NY.
Rosenwasser
M P
MP
Ratcliffe
A
A
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D046508:Culture Techniques; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008666:Metalloendopeptidases / Q000378:metabolism*; D009288:Naproxen / Q000494:pharmacology*; D011509:Proteoglycans / Q000187:drug effects / Q000378:metabolism*
D006025:Glycosaminoglycans; D007375:Interleukin-1; D011509:Proteoglycans; D009288:Naproxen; D008666:Metalloendopeptidases