Comparison of the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on proteoglycan synthesis by articular cartilage explant and chondrocyte monolayer cultures

Abstract

Experiments were conducted to study proteoglycan biosynthesis by rabbit articular chondrocytes cultured in the presence of NSAIDs and 35SO 2− 4 for up to 8 days. Both articular cartilage explants and confluent chondrocyte monolayer culture models were used. Medium was changed every 2 days and the [ 35SO 4]proteoglycans which had accumulated in the medium and the extracellular matrix during the culture intervals were assayed separately. In long-term experiments, drugs were removed on day 8, and proteoglycan production during a 10–12 day culture interval also was assayed. The drugs studied were diclofenac, indomethacin, ketoprofen, piroxicam and tiaprofenic acid, at concentrations of 0, 0.1, 1, 10, 50 and 100μg/mL. Whereas proteoglycan production by cell cultures was maximal early in the culture period, explants produced more proteoglycans as time progressed. The highest concentrations of all of the drugs, especially diclofenac and indomethacin, inhibited proteoglycan secretion by both cell and explant cultures. However, after removal of the drugs from the cultures, suppressed proteoglycan production reversed to levels equivalent to, or higher than controls in the cell cultures, but largely persisted in explant cultures. About 70–80% of proteoglycans produced by explants were retained in the matrix, whereas about 80–90% of proteoglycans produced by cell cultures were secreted into the medium. Where drugs inhibited proteoglycan production, the levels were reduced by approximately the same proportions in both extracellular matrix and culture medium fractions. Of the NSAIDs examined only ketoprofen demonstrated a stimulatory effect on PG synthesis in explant cultures at a physiological concentration (0.1μg/mL).