Effects of MTX, CS12192, or the combination of CS12192 and MTX treatments on cartilage destruction determined by safranin O-fast green staining and real-time PCR in joint tissues of CIA rats on day 28. (A,B) The safranin O-fast green staining joint tissue sections of knee (the red arrows are cartilage destruction areas) (A) and ankle (B). The cartilage destruction scores were measured as described in the Methods and are presented as the mean ± SEM from groups of 10 rats. Scale bar, 50 µM. (C) Real-time PCR analysis for relative mRNA expression of COMP, MMP-9, TIMP-1 and IL-1R in synovial tissues of CIA rats in response to different treatments. Results are presented as the mean ±SEM from groups of 10 rats. * p < 0.05; ** p < 0.01; and *** p < 0.001 as indicated.