Calcium response via CRAC channels in human synovial cells induced by shear stress in rheumatoid arthritis

The role of calcium release-activated calcium channel (CRAC) inhibitors in the pathogenesis of rheumatoid arthritis (RA) is unclear. We focused on stromal interaction molecule 1 (STIM1) and Ca²⁺ release-activated channel regulator 2 A (CRACR2A), which participate in CRAC activation, to understand the signaling mechanism of human RA fibroblast-like synovial (FLS) cells in response to shear stress (SS). Human normal and RA FLS cell cultures were studied. The rates of intracellular calcium release and extracellular calcium influx in response to SS differed, and the responses to the first and second stimuli were analyzed. In the RA FLS cells, CRAC inhibitor significantly decreased the second/first stimulus ratio compared with that of the normal cells, and STIM1 and CRACR2A exhibited significantly increased expression levels compared with those in the normal FLS cells. Therefore, STIM1 and CRACR2A expression and Ca²⁺ influx in FLS cells are implicated in the pathogenesis of RA.