Peripheral Circadian Rhythms Disrupted Relative to the Central Circadian Regulator in a Mouse Model of Inflammatory Arthritis
Objective: To investigate the effects of inflammatory arthritis on circadian rhythms and locomotor activity in a mouse model of rheumatoid arthritis.
Approach: Mouse Model: Utilized the K/BxN serum transfer arthritis (STA) mouse model to study the progression of rheumatoid arthritis.Locomotion Monitoring: Employed continuous actigraphy using passive infrared sensors to monitor locomotion throughout the disease course.DEX Treatment: Administered dexamethasone (DEX) to assess its impact on disease progression and circadian rhythms.Ankle Thickness Measurement: Measured ankle thickness to evaluate disease activity and progression.Bioluminescence Studies: Conducted bioluminescence studies on tissue-specific circadian clocks in response to inflammatory arthritis.Key Findings: Total daily activity serves as a sensitive measure of disease state in inflammatory arthritis. Inflammatory arthritis disrupts local circadian clocks in affected joints while preserving central diurnal timing. Locomotion declines during arthritis, indicating reduced daily movement. Interpretation: The study indicates that while central circadian rhythms remain intact, local disruptions occur in the circadian clocks of arthritic joints.
Limitations: The study primarily uses a mouse model, which may not fully replicate human RA. Methodological approaches may limit the ability to capture the full diurnal nature of the disorder. Conclusion: Continuous monitoring of locomotor activity provides insights into the progression of inflammatory arthritis.