Thus, it was noteworthy that Thiel et al. [133] showed that PD184352, another small molecule inhibitor of upstream MEK whose activation is required for ERK1/2 to be phosphorylated, inhibited paw edema and the severity of arthritis in a collagen-induced arthritis model in DBA/1LacJ mice. This evidence concerns the gene MAPK3 and arthritic joint disease.