【Animal modeling】-Comparative study on the establishment of rabbit knee osteoarthritis model by modified Hulth method and type Ⅱ collagenase injection method

  Objective To compare and analyze the differences between two common modeling methods for rabbit knee osteoarthritis models, and to provide reference for the selection of different types of knee osteoarthritis animal models.

  Methods Nine healthy New Zealand white rabbits were randomly divided into 3 groups: blank group, modified Hulth group and collagenase group. The modified Hulth group and the collagenase group were given the modified Hulth method and intra-articular injection of collagenase, respectively, and they were encouraged to move every day after 1 week. Lequesne MG score, X-ray, Micro-CT, and Pelletier score were performed after 6 weeks. , Mankin score, ELISA test, observe the general and pathological changes of knee joint.

  Results Compared with the blank group, the surface of the knee articular cartilage of the rabbits with both modeling methods showed defects; the pathological results showed that the cartilage layer had cracks, the staining of safranin O was reduced, the tide line was distorted and blood vessels passed through; ELISA results showed that the blank group , the serum levels of TNF-α in the improved Hulth group and collagenase group were (624.99±17.82), (1140.56±129.81) and (1480.69±492.08) pg/mL, respectively. The levels of IL-1β in serum were (30.23±0.25), (46.67±0.71) and (46.82±1.04) pg/mL, respectively. Compared with the blank group, the difference was statistically significant (all P<0.05). In addition, the knee joint in the modified Hulth group was accompanied by osteophyte formation, and the cartilage damage of the femoral medial condyle was more serious, while the damage site of the collagenase group was mainly the tibial medial condyle.

  Conclusion Both modeling methods can construct an ideal KOA model. The injury degree of the modified Hulth method was more serious; the collagenase-induced injury model was closer to the process and pathogenesis of human KOA.