AP-1 pathway: Stromal cell-derived factor (SDF)-1, significantly higher in RA, acts through CXCR4 to activate ERK and the downstream transcription factors (c-Fos and c-Jun), resulting in the activation of AP-1 on the MMP promoter and contributing to MMP secretion of chondrocytes [81]. This evidence concerns the gene FOS and rheumatoid arthritis.