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Detailed information of patients with RA enrolled in this study. Joint samples obtained from 10 different patients to establish primary cultured synovial fibroblast cell lines. Age, sex, disease duration, CRP, DAS28-ESR, and treatment with MTX, PSL, and other DMARDs shown in the table. (PDF 252 kb)

The mRNA expression of circadian clock genes over time. mRNA expression of circadian clock genes measured at â 4 h (before synchronization), 0 h (just before MTX stimulation), 24 h, 32 h, and 48 h. Controls and 10/100 nM of MTX showed almost the same expression rhythms, and MTX influenced their expression levels. (PDF 264 kb)

Cell viability of MTX-treated fibroblasts. Cell viability of RA synovial fibroblasts measured by WST-8 assay after 24 h of stimulation of MTX (1 pM to 1 ÎźM). MTX (1 and 10 nM) significantly decreased cell viability as shown in Fig. 1, while 1â 100 pM of MTX did not. (PDF 274 kb)

Among the symptoms of patients with rheumatoid arthritis (RA), joint stiffness is influenced by diurnal rhythm and reaches peak in the morning, which is a common complaint and reflects the circadian nature of disease manifestation. In addition, inflammatory cytokines, which reach peak secretion early in the morning are major players causing the morning stiffness. In this review, we explore the link between the circadian clock and inflammation, focusing on the interactions of various clock genes with the immune-pathways underlying the pathology of rheumatoid arthritis.