Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting joints marked by daily and intermittent surges in inflammatory cytokine levels that result in “flares” of disease activity. Because circadian proteins regulate inflammatory responses in arthritis, continuous behavioral and tissue-level monitoring may clarify therapeutic dynamics. Using the K/BxN serum transfer arthritis (STA) mouse model, we tested whether locomotor activity and circadian clock gene expression track RA progression from onset through symptom resolution.
Methods: C57BL/6NJ and PER2::Luc mice (8-10 weeks) received 180 μL K/BxN serum via retroorbital injection. Uninjected littermates served as controls. We measured daily ankle thickness and continuously monitored open-field locomotion from singly-housed mice, a subset of which received dexamethasone (DEX) at dusk daily for six days. PER2::LUC bioluminescence from paw, suprachiasmatic nuclei (SCN), and femoral heads explants from mice treated with or without DEX was compared during STA.
Results: Total daily locomotion decreased alongside ankle swelling ~2 days following K/BxN STA. STA altered the timing of daily PER2 peak expression in arthritic paws, but not in SCNs or nonarthritic joints. By day 22, total daily locomotion, ankle thickness, and paw circadian phase had resolved. In vivo DEX reduced circadian phase disruption in arthritic paws, accelerated the resolution of ankle swelling, and increased total daily locomotion without altering locomotor timing.
Conclusions: Locomotor activity provides real-time, non-invasive measurement of RA onset and spontaneous or therapeutic resolution. Altered PER2 expression indicates local circadian synchrony in arthritic joints is impaired. DEX may aid recovery by resynchronizing circadian rhythms in arthritic tissues.
