Effects of the selective EP4 antagonist, CJ‐023,423 on chronic inflammation and bone destruction in rat adjuvant‐induced arthritis

Prostaglandin E 2 (PGE 2 ) produced by cyclooxygenase (COX) is a potent pro-inflammatory mediator. We have recently discovered CJ-023,423, a highly selective antagonist of EP 4 receptors, one of the PGE 2 receptors. This agent is suitable for exploring the effects of blocking EP 4 receptors following oral administration in rats. In this study, CJ-023,423 was used in rats with adjuvant-induced arthritis (AIA) to investigate the role of the EP 4 receptor in chronic inflammation and bone destruction. These effects were compared with those of rofecoxib, a selective COX-2 inhibitor. CJ-023,423 had significant inhibitory effects on paw swelling, inflammatory biomarkers, synovial inflammation and bone destruction in AIA rats. In particular, the inhibitory effect on paw swelling in AIA rats was comparable to that of rofecoxib. These results suggest that PGE 2 acting via the EP 4 receptor is involved in the development of chronic inflammation and bone destruction, particularly with respect to oedema in AIA rats. This is the first study to confirm the in-vivo effects of EP 4 receptor blockade on inflammation and bone destruction in AIA rats with a small-molecule compound.