Fig. 1

Experimental protocols. a Experiment 1. Collagen-induced arthritis (CIA) was induced in mice by a first injection of bovine type II collagen (bCol II) with complete Freund’s adjuvant (CFA) on day 0 and a booster injection on day 21 (black arrows). The control groups were injected with saline or CFA. The mice were single-housed in home cages with running wheels from day 16, and the number of wheel rotations was measured continuously (voluntary wheel running test). The arthritis score was checked on days 21, 24, 26, 28, 31, 33, 35, 38, 40, and 42 (open triangles). b Experiment 2. CIA was induced by a first injection of bovine type II collagen/CFA on day 0 and a booster injection on day 21. The CIA mice received tofacitinib 15 mg/kg/day or vehicle (PEG300) by subcutaneous osmotic pump infusion from day 16 (blue arrow). A voluntary wheel running test was performed from day 16 onwards. The arthritis score was assessed on days 19, 21, 24, 26, 28, 31, 33, 35, 38, 40, and 42 (open triangles). c Experiment 3. Each model was created in the same way as for experiment 1. The temperature preference test was performed on days 19, 24, 28, 33, 38, and 42 (open arrows) after habituation on day 17 (gray arrow). The arthritis score was assessed on days 19, 21, 24, 26, 28, 31, 33, 35, 38, 40, and 42 (open triangles). d Experiment 4. Induction of CIA and drug administration were performed in the same way as in experiment 2. The temperature preference test was performed on days 19, 24, 28, 33, 38, and 42 (open arrows) after habituation on day 17 (gray arrow). The arthritis score were assessed on days 19, 21, 24, 26, 28, 31, 33, 35, 38, 40, and 42 (open triangles)