Rheumatoid Arthritis and Circadian Rhythm

Characteristic features of rheumatoid arthritis (RA) include the production of proinflammatory cytokines and disease-specific auto-antibodies and the manifestation of disease symptoms in a circadian pattern, typified by morning stiffness. The pathogenesis of RA involves the activation of the proto-oncogene c-Fos and the cell cycle regulator Weel kinase, which cause synovial cellular overgrowth leading to characteristic "tumor-like" and arthritic joint destruction. It has been reported that in mice genetically deleted for cryptochrome (Cry) 1/2, circadian clock genes that directly regulate circadian rhythm, free-running rhythmicity is abolished and Weel kinase is constitutively upregulated. Therefore, to examine more closely the potential circadian regulation of rheumatoid arthritis, we induced experimental arthritis in Cry knockout mice and observed an interplay between Cry gene activity and proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) production. Thus, the biological clock and arthritis influence each other, and a further understanding of this interplay could lead to treatments that may improve the activity of daily living (ADL) of patients with RA.