New potential therapeutic approaches targeting synovial fibroblasts in rheumatoid arthritis

Synovial cells play a key role in joint destruction during chronic inflammation. In particular, activated synovial fibroblasts (SFs) undergo intrinsic alterations leading to an aggressive phenotype mediating cartilage destruction and bone erosion in rheumatoid arthritis (RA). Recent research has revealed a number of targets to control arthritogenic changes in SFs. Therefore, identification of SF phenotypes, control of epigenetic changes, modulation of cellular functions, or regulation of the activity of cation channels and different signaling pathways has been investigated. Although many of these approaches have shown efficacy in vitro and in animal models of RA, further research is needed to select the most relevant targets for drug development. This review is focused on the role of SFs as a potential strategy to discover novel therapeutic targets in RA aimed at preserving joint architecture and function.