Moreover, inducing the expression of GADD45 in FLS resulted in the reduction of TNF-induced signalling and decreased expression of MMPs [56], whereas the absence of GADD45 by knockout worsened K/BxN serum-induced arthritis in mice, leading to a significant increase in JNK pathway signalling, elevated expression of MMP3 and MMP13 genes in the joints and an expansion of the inflammation area [56]. This evidence concerns the gene MAPK8 and arthritic joint disease.