Objective: To study the effects of Zhengqing Fengtongning Tablet (ZFT) and methotrexate (MTX) on the expression of osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL), and interleukin 17 (IL-17) in collagen-induced arthritis (CIA) rats, thus addressing their bone protection.
Methods: The CIA rat model was established by intradermally injecting type II collagen emulsion from the rats' back and tail. Totally 28 successfully modeled rats [with the arthritis index (AI) more than 2] were randomly divided into the model group, the Chinese medicine (CM) treatment group, the MTX group, and the ZFT + MTX treatment group, 7 rats in each group. Another 7 rats were recruited as the normal control group. Rats were administered from the 7th day of modeling. Rats in the MTX group were treated with MTX at 3.8 mg/kg once a week. Those in the CM group were treated with ZFT at the daily dose of 130 mg/kg, once a day. Those in the ZFT + MTX treatment group were treated with both MTX (at 3.8 mg/kg once a week) and ZFT (at the daily dose of 130 mg/kg, once a day). Those in the model group and the normal control group were administered with normal saline of the equal volume by gastrogavage. All the intervention lasted for 26 days. The destruction of joints in the four limbs were observed using X-ray. The AI was recorded. The expression levels of serum OPG, RANKL, and IL-17 were detected at the end of the experiment.
Results: During the whole process, all rats except those in the model group were in a good condition. On the 21st day of modeling the AI of all rats reached the peak, but it decreased after treatment. Compared with the model group, the AI decreased in the CM treatment group, the MTX group, and the ZFT + MTX treatment group with statistical difference (P < 0.05). Compared with the model group, the OPG increased and RANKL decreased in the MTX group; the OPG and OPG/RANKL increased in the CM treatment group; the OPG, RANKL, and OPG/RANKL increased, and IL-17 decreased in the ZFT + MTX treatment group, all showing statistical difference (P < 0.05). Compared with the MTX and the ZFT + MTX treatment group, OPG/RANKL increased and IL-17 decreased in the ZFT + MTX treatment group (both P < 0.05).
Conclusion: ZFT + MTX could synergistically elevate peripheral OPG/RANKL and down-regulate IL-17 in CIA model rats.