Drug effects on a novel in vitro model of cartilage breakdown.

Abstract

A new in vitro model for studying cartilage breakdown has been utilised in this work. Polymorphonuclear neutrophils (PMNs) with phorbol myristate acetate (PMA) were layered onto 2 microns cryostat sections of bovine nasal cartilage. After incubation, the sections were fixed, stained, and the amount of glycosaminoglycan (GAG) contents measured by microdensitometry. PMNs caused GAG loss from sections and this was greatly enhanced when the PMNs were activated by PMA. Various pharmacological agents were then added to the system, namely acetyl salicylic acid, indomethacin, ibuprofen, piroxicam, dexamethasone, D-penicillamine, chloroquine and BN50548. The drugs tested had no direct effect on cartilage matrix, nor did they affect GAG loss from sections treated with non-stimulated PMNs. However, BN50548, a novel protease inhibitor, afforded a dose response protection of cartilage section from GAG loss by PMA stimulated PMNs. This model may prove to be of value in screening novel antiproteases with chondroprotective activity.