Abstract: BACKGROUND: The two methods commonly used for preparing animal models of knee osteoarthritis are surgical trauma and intra-articular injection of protease. However, the models induced by intra-articular injection of drugs are not stable, the traditional surgical modeling method has great damage to the knee joint, and the modeling process differs greatly from the development of clinical knee osteoarthritis.
OBJECTIVE: To evaluate the best preparation method for the animal model of knee osteoarthritis through establishing a rabbit knee osteoarthritis model by injuring the knee joint in different surgical ways. 
METHODS: Sixteen male New Zealand white rabbits aged 5-6 months were randomly divided into sham operation group, model group A, model group B and model group C, with four rats in each group. In the sham operation group, the medial side of the right knee joint was incised and immediately sutured. In the model group A, the meniscus and anterior cruciate ligament of the right knee were worn. In the model group B, the meniscus of the right knee joint was removed and the anterior cruciate ligament of the right knee was worn. In the model group C, the right knee meniscus was removed and the anterior cruciate ligament of the right knee joint was transected. Antibiotics were injected for 3 consecutive days after operation, and the general conditions were recorded. After 4 weeks, the knee joints were observed by X-ray, the changes of cartilage tissue were observed by hematoxylin-eosin staining, and the levels of inflammatory factors in the synovial fluid and serum of the right knee were detected by enzyme-linked immunosorbent assay.
RESULTS AND CONCLUSION: Redness, swelling and heat pain were evident in the right knee joint of the model group, and the skin temperature in the model groups was significantly higher than that in the sham operation group. Postoperative skin temperature of the right knee joint in the model groups was significantly higher than that in the sham operation group (P < 0.05). The X-ray observation showed no abnormalities in the knee joint in the sham operation group, while the model groups showed varying degrees of articular surface destruction and joint space narrowing, with the model group C being the most severe. Hematoxylin-eosin staining showed normal cartilage tissue in the sham-operated group, while the model groups showed a reduction in the number of chondrocytes with disordered structural levels. In the model group C, the cartilage structure was seriously damaged with angiogenesis being visible. Enzyme-linked immunosorbent assay showed that serum inflammatory factor levels in the model groups were significantly higher than those in the sham operation group (P < 0.05). The level of inflammatory factors in the synovial fluid of the right knee joint was significantly higher in the model groups than the sham operation group (P < 0.05). To conclude, through the analysis of the general condition, imaging and related factors of the knee joint of each group, it was found that the above three surgical methods of the knee injury could successfully construct the rabbit knee osteoarthritis model. The model group C reached the middle and late stage of knee osteoarthritis and the model groups A and B were consistent with the changes in early and middle knee osteoarthritis. In addition, this experiment confirmed that the speed of knee osteoarthritis progression is positively correlated with the degree of knee injury, and the level of inflammatory factors in serum is more sensitive to the changes of knee osteoarthritis than that in the synovial fluid.

Key words: knee osteoarthritis, animal model, inflammation, joint effusion, cartilage