Furthermore, MMPs have been demonstrated to be implicated in the pathophysiology and pharmacology of RA, with significant over-expression of MMP1, MMP3, MMP7, MMP8, MMP9, MMP12, MMP13, MMP19, and MMP25, and a concurrent downregulation of MMP17, MMP24, and MMP28. This evidence concerns the gene MMP28 and rheumatoid arthritis.