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

Authors
 Minjeong Ji  ;  Hee Jung Ryu  ;  Hyeon-Man Baek  ;  Dong Min Shin  ;  Jeong Hee Hong 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.54(4) : 503-517, 2022-04 
Journal Title
EXPERIMENTAL AND MOLECULAR MEDICINE
ISSN
 1226-3613 
Issue Date
2022-04
MeSH
Animals ; Arthritis, Experimental* / drug therapy ; Arthritis, Rheumatoid* ; Cell Movement / physiology ; Cell Proliferation ; Cells, Cultured ; Disease Models, Animal ; Fibroblasts / metabolism ; Humans ; Mice ; Synovial Membrane / metabolism ; Synoviocytes* / metabolism ; Tumor Necrosis Factor-alpha / metabolism
Abstract
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-α 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-α, 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.
Files in This Item:
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DOI
10.1038/s12276-022-00756-6
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Shin, Dong Min(신동민) ORCID logo https://orcid.org/0000-0001-6042-0435
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/188756
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