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).