Dynamic synovial fibroblasts are modulated by NBCn1 as a potential target in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease characterized by aggressive fibroblast-like synoviocytes (FLSs) and pannus formation. Various therapeutic strategies have been developed against inflammatory cytokines in RA in recent decades. Based on the migratory features of FLSs, we examined whether modulation of the migratory module attenuates RA severity. In this study, inflamed synovial fluid-stimulated FLSs exhibited enhanced migration and migratory apparatus expression, and sodium bicarbonate cotransporter n1 (NBCn1) was identified in primary cultured RA-FLSs for the first time. The NBC inhibitor S0859 attenuated the migration of FLSs induced with synovial fluid from patients with RA or with TNF-alpha stimulation. Inhibition of NBCs with S0859 in a collagen-induced arthritis (CIA) mouse model reduced joint swelling and destruction without blood, hepatic, or renal toxicity. Primary FLSs isolated from the CIA-induced mouse model also showed reduced migration in the presence of S0859. Our results suggest that inflammatory mediators in synovial fluid, including TNF-alpha, recruit NBCn1 to the plasma membrane of FLSs to provide dynamic properties and that modulation of NBCn1 could be developed into a therapeutic strategy for RA. Rheumatoid arthritis: A potential protein target for treatment A protein which transports ions across cell membranes has been implicated in promoting destructive cellular activities in joints affected by rheumatoid arthritis (RA) and could become a target for new drugs to treat RA. Researchers in South Korea led by Jeong Hee Hong at Gachon University, Incheon, and Dong Min Shin at Yonsei University, Seoul, identified the protein NBCn1 in fibroblast-like synoviocytes (FLS) with response to the synovial fluid of patients' joints affected by RA. Chemical signals associated with RA enhanced the activity of NBCn1 in FLS cells, promoting the cell migration that leads to joint damage. Mouse studies revealed that inhibiting NBCn1 activity reduced the cellular signals and interactions that damage joints, leading to less swelling and tissue destruction. Drugs that reduce NBCn1 activity could therefore offer new opportunities to treat RA.

Automated summary

The study found that modulation of the migratory module of fibroblast-like synoviocytes (FLSs) can attenuate the severity of rheumatoid arthritis (RA). The sodium bicarbonate cotransporter n1 (NBCn1) was identified in RA-FLSs and inhibiting NBCs reduced FLS migration and RA symptoms.