Effects of therapeutic treatment with AZM in arthritis models
We next determined the impact of AZM in mouse model of rheumatoid arthritis: CIA. Compared with solvent-treated ones, AZM-treated mice showed dose-dependent amelioration with a marked decrease in arthritis score (Fig. 2A), thickness (Fig. 2B) and paw swelling (Fig. 2C). Histological analysis of affected joints from AZM-treated mice revealed reduced evidence of synovial hyperplasia, cartilage degradation and bone destruction (Fig. 2D). The score data showed that the degree of inflammation, synovial hyperplasia, cartilage degradation and bone destruction were reduced in AZM treated mice (Fig. 2E). In addition, AZM-treated CIA mice displayed reduced levels of bone erosion and destruction (Fig. 2F), as evidenced by the increase in BV/TV, Tb. BMD, Tb. Th and Tb. N but decrease in Tb. Sp in the distal tibia (Fig. 2G). Mice treated with AZM also had significantly decreased serum levels of proinflammatory cytokines interleukin (IL)-1β and IL-6, and COMP, and elevated levels of anti-inflammatory cytokines IL-10 and IL-13, when compared with control mice (online Supplementary Fig. 3). Additionally, AZM treatment decreased the RANKL level and increased the OPG/RANKL ratio (online Supplementary Fig. 3).