The therapeutic effect of tacrolimus on inflammation and bone erosion in a serum-induced arthritis mouse model. (A) Before immunization of C57BL/6 mice with K/BxN serum, tacrolimus (1 mg/kg) was intraperitoneally introduced four times for a week. At day 10, the experimental mice were sacrificed. Serum-induced arthritic mice pretreated with tacrolimus showed less paw swelling compared to those not treated with tacrolimus. Histological findings demonstrated protection against joint damage in the cartilage, bone, and synovium of tacrolimus-treated mouse joints. (B) Ankle thickness in the tacrolimus-treated mice was significantly less than that of non-treated serum-induced arthritis mice on days 8 and 10 (*P <0.05). (C) Semi-quantitative analysis for inflammation and bone erosion indicated fewer inflammatory changes and less bone destruction in tacrolimus-treated mice compared to untreated mice (*P <0.05). (D) Tacrolimus treatment significantly reduced RANKL mRNA expression in the affected joints of mice with serum-induced arthritis (*P <0.05). In contrast, the reduction in OPG mRNA expression in serum-induced arthritis was reversed with treatment by tacrolimus (*P <0.05). SOCS3 mRNA expression also was increased in arthritic joints treated with tacrolimus (*P <0.05 versus serum-induced arthritis not treated with tacrolimus). OPG, osteoprotegerin; RANKL, receptor activator of NF-κB ligand; SIA, serum-induced arthritis; SOCS3, suppressor of cytokine signaling 3; Tac, tacrolimus.