role of fibroblast activation protein alpha in fibroblast-like synoviocytes of rheumatoid arthritis

Fibroblast-like synoviocytes (flss) have been introduced in recent years as a key player in thepathogenesis of rheumatoid arthritis (ra), but the exact mechanisms of their transformation andintracellular pathways have not yet been determined. this study aimed to investigate the role offibroblast activation protein-alpha (fap-α) in the regulation of genes involved in thetransformation and pathogenic activity of ra flss.synovial flss were isolated from ra patients and non-arthritic individuals (n=10 in bothgroups) and characterized; using immunocytochemistry and flow cytometry analysis. flss weredivided into un-treated and talabostat-treated groups to evaluate the fap-α effect on the selectedgenes involved in cell cycle regulation (p21, p53, ccnd1), apoptosis (bcl-2, puma), andinflammatory and destructive behavior of flss (il-6, tgf-β1, mmp-2, mmp-9, p2rx7). geneexpression analysis was performed by quantitative real-time polymerase chain reaction (qrtpcr),and immunoblotting was carried out to evaluate fap-α protein levels. the basal level of fap-α protein in ra patients was significantly higher than non-arthritic control individuals. however, no differences were observed between ra and non-arthritic flss,at the baseline mrna levels of all the genes. talabostat treatment significantly reduced fap-α protein levels in both ra and non-arthritic flss, however, had no effect on mrnaexpressions except an upregulated tgf-β1 expression in non-arthritic flss.a significantly higher protein level of fap-α in flss of ra patients compared with thatof healthy individuals may point to the pathogenic role of this protein in ra flss. however, more investigations are necessary to address the mechanisms mediating the fap-α pathogenic role in ra flss.