Misoprostol, a PGE2 analog binding to EP2, EP3, and EP4 receptors, exacerbated collagen-induced arthritis in mice through activating the inflammatory IL-23/IL-17 axis, whereas an EP4-receptor antagonist reduced arthritis in a mouse model (Sheibanie et al., 2007a; Chen et al., 2010). This evidence concerns the gene PTGER2 and arthritic joint disease.