Effect of carprofen on sulfated glycosaminoglycan metabolism, protein synthesis, and prostaglandin release by cultured osteoarthritic canine chondrocytes.

OBJECTIVE

To determine whether the nonsteroidal anti-inflammatory drug carprofen directly influences canine chondrocyte metabolism.

ANIMALS

Cartilage from the femoral heads of 13 dogs undergoing total hip replacement.

PROCEDURE

Rates of glycosaminoglycan (GAG) synthesis and degradation, protein synthesis, cell viability, and prostaglandin release were determined in canine explant cartilage or monolayer canine chondrocyte cultures in the presence of 0 to 100 micrograms of carprofen/ml. Rate of GAG synthesis was assessed as incorporation of [35S]sulfate into cartilage matrix during a 3-hour pulse label. Degradation of cartilage GAG was assessed as rate of release of [35S]sulfate from prelabeled explant cultures. Rates of total protein synthesis were assessed as incorporation of [35S]methionine into trichloracetic acid precipitable material during a 3-hour pulse label. Radiolabeled chondrocyte proteins were separated by polyacrylamide gel electrophoresis and visualized by fluorography. Rates of prostaglandin E2 release were assessed by radioimmunoassay.

RESULTS

Carprofen stimulated a significant increase in the rate of GAG synthesis at concentrations of 1 and 10 micrograms/ml, with no change in total protein synthesis, pattern of new protein synthesis, or cell viability. At concentration > or = 20 micrograms/ml, inhibition of GAG synthesis and total protein synthesis was observed. There was no significant change in rate of release of GAG from cartilage explants, but potent inhibition of prostaglandin release was observed.

CONCLUSIONS

Carprofen has a direct influence on chondrocyte activity, resulting in changes in rate of production of cartilage matrix.

CLINICAL RELEVANCE

In determining the optimal therapeutic dose of carprofen for arthritic conditions in dogs, it is important to consider potential influences on cartilage, as well as anti-inflammatory actions.