Cathepsins are an extensive family of cysteine proteases that have broad proteolytic activity, including activity on types II, IX, and XI collagen and proteoglycans. Like MMPs, the cathepsins are regulated by cytokines and by proto-oncogenes such as Ras. IL-1 and TNF induce cathepsin L expression in cultured FLS. In situ hybridization studies demonstrate cathepsin B and L RNA transcripts in RA synovium, especially at sites of erosion. A ribozyme that cleaves cathepsin L decreases FLS invasion and cartilage destruction in the SCID mouse model with implanted cultured synoviocytes, which suggests that this protease has clinical relevance.