CTSS and rheumatoid arthritis: Fibroblasts are major contributors to synovial inflammation and bone/cartilage destruction and are dominant producers of a variety of cytokines, especially IL-6 in RA, FLSs-derived IL-6 also regulates the production of matrix enzymes, such as matrix metalloproteins (MMPs), aggrecanases and cathepsins, aggravating articular damage (McInnes and Schett, 2007; Nguyen et al., 2017).