This study investigated the release of prostaglandin E2 (PGE2) from cartilage following an impact load in vitro and the possible chondroprotective effect of cyclooxygenase-2 (COX-2) inhibition using non-steroidal anti-inflammatory drugs (NSAIDs).
Explants of human articular cartilage were subjected to a single impact load in a drop tower, and then cultured for 6 days in the presence of either a selective COX-2 inhibitor (celecoxib; 0.01, 0.1, 1.0 and 10 μM) or a non-selective COX inhibitor (indomethacin; 0.1 and 10 μM). The concentrations of PGE2 and glycosaminoglycans (GAGs), a measure of cartilage breakdown, were measured in the explant culture medium at 3 and 6 days post-impact. Apoptotic cell death was measured in frozen explant sections by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) method.
PGE2 levels were increased by more than 20-fold in the medium of explants at both 3 (p = 0.012) and 6 days (p = 0.004) following impact, compared with unloaded controls. In the presence of celecoxib and indomethacin, the PGE2 levels were reduced in a dose-related manner. These inhibitors, however, had no effect in reducing the impact-induced release of GAGs from the cartilage matrix. Addition of celecoxib and indomethacin significantly reduced the number of trauma-induced apoptotic chondrocytes in cartilage explant sections.
In this study, a marked increase in PGE2 was measured in the medium following an impact load on articular cartilage, which was abolished by the selective COX-2 inhibitor, celecoxib, and non-selective indomethacin. These inhibitors reduced chondrocyte apoptosis but no change was observed in the release of GAGs from the explants, suggesting that the COX/PGE2 pathway is not directly responsible for cartilage breakdown following traumatic injury. Our in vitro study demonstrates that it is unlikely that COX-2 inhibition alone would slow down or prevent the development of secondary osteoarthritis.