The Vitamin D Receptor Regulates Rheumatoid Arthritis Synovial Fibroblast Invasion and Morphology

摘要: Serum levels of vitamin D are commonly reduced in patients with rheumatoid arthritis (RA) and have been implicated disease pathogenesis. We recently identified a new receptor transcriptional signature synovial tissues from rats mild nonerosive arthritis, suggesting D-mediated protective effect. In the present study, we address hypothesis that part effect is mediated via interference fibroblast-like synoviocyte (FLS) invasive properties, an vitro cellular phenotype correlates radiographic histological damage pristane-induced RA. FLSs derived DA RA were studied model invasion through collagen-rich barrier (Matrigel) over 24-h period, presence or absence calcitriol, active form D. Matrix metalloprotease (MMP) expression analyzed zymography quantitative real-time polymerase chain reaction, cytoskeleton was immunofluorescense microscopy. Calcitriol significantly inhibited FLS by 54% 53%, respectively. also interleukin (IL)-1β-induced MMP-1 95% 73.5% FLS. treatment actin reorganization, polarized formation lamellipodia colocalization phosphorylated focal adhesion kinase (p-FAK) lamellipodia, all consistent cell ability to move invade. conclusion, calcitriol invasion. This discovery suggests serum its metabolites seen might increase risk for FLS-mediated cartilage bone erosions. Treatment analogs has potential become helpful adjuvant aimed at preventing reducing joint destruction.