Objectives: We aimed to define the importance of transient receptor potential canonical 6 (TRPC6) expression and function in fibroblast-like synoviocytes (FLSs) and to investigate the contribution of TRPC6 in the model of rheumatoid arthritis (RA).
Methods: We compared TRPC6 expression levels in FLSs from RA patients (RA-FLSs), and in FLSs from osteoarthritis (OA) patients (OA-FLSs). By using vitro functional assays which united with small interfering RNA-induced knockdown and functional modulation of TRPC6 in RA-FLSs. Finally, we confirmed the effectiveness of regulating TRPC6 in a collagen induced arthritis (CIA) mice model.
Results: We found that FLSs expressed the TRPC6 as their major Transient receptor potential canonical channel. Both mRNA and protein expression of TRPC6 were found somewhat higher levels in RA-FLSs than in OA-FLSs. Moreover, inhibiting expression of TRPC6 in vitro reduced proliferation of, as well as inflammatory mediator and protease production by, RA-FLSs, whereas opening native TRPC6 enhanced both proliferation and inflammatory mediator of RA-FLSs. Additionally, a TRPC6 deficiency in mice blunted the development of experimental RA, CIA models, reduced joint and bone damage, and inhibited FLS invasiveness and proliferation.
Conclusions: Our results demonstrated a critical role of TRPC6 in regulating FLSs mediated inflammation. Therefore, TRPC6 represents potential therapeutic targets in RA.