Suppression of proteoglycan synthesis in chondrocyte cultures derived from canine intervertebral disc

Chondrocytes were dissociated enzymatically from canine nucleus pulposus. After attaining monolayer growth, the cells were subpassaged and incubated with sodium salicylate, indomethacin, or sodium meclofenamate (10(-2) M to 3 x 10(-6) M). When incubated with nonsteroidal anti-inflammatory drug concentrations mimicking therapeutic plasma levels, proteoglycan synthesis was significantly suppressed. After 24 hours of incubation, there was a 15% decrease in radioactive sulfate (35SO4) incorporation for salicylate (10(-3) M), a 29% decrease for indomethacin (3 x 10(-6) M), and a 75% decrease for sodium meclofenamate (10(-5) M). This inhibition was both dose- and time-dependent. Despite the effect of these nonsteroidal anti-inflammatory drugs on quantitative proteoglycan synthesis, there was no demonstrable effect of these drugs on the size of proteoglycan monomers or the degree to which proteoglycan aggregate formation occurred.