Abstract:

BACKGROUND: Studies have shown that cornuside I (Cor I) can promote the proliferation of osteoblasts and chondrocytes, but its role and mechanism in repairing early cartilage damage of knee osteoarthritis are not clear.

OBJECTIVE: To investigate the effect of Cor I on knee osteoarthritis rats and its effect on interleukin-6 (IL-6)/JAK2/STAT3 signaling pathway. 
METHODS: Fifty healthy male Sprague-Dawley rats were randomly divided into sham operation group, knee osteoarthritis model group (model group), Cor I high-dose group (Cor I-H), and cornuside I low-dose group (Cor I-L) and positive control group (celecoxib), with 10 rats in each group. Except the sham operation group, the knee osteoarthritis rat model was prepared according to the Hulth method. The Cor I-L and Cor I-H groups were administrated with Cor I 1.25 and 5 g/kg once a day for 6 weeks after modeling. The positive control group was fed with 4 mg/kg celecoxib, and the sham operation and model groups were fed with the same amount of normal saline once a day. The rats were sacrificed by cervical dislocation 24 hours after the last administration. Hematoxylin-eosin staining was used to observe the pathological and morphological changes of articular cartilage tissue in rats, and the degree of cartilage degeneration  was scored according to Mankin’s method. Interleukin-1β, tumor necrosis and matrix metalloproteinase-13 in rat cartilage tissue were detected by ELISA. Interleukin-6 and STAT3 protein expression in rat articular cartilage tissue were detected by immunohistochemistry. Relative expressions of JAK2, p-JAK2, STAT3, and p-STAT3 were detected by western blot. 
RESULTS AND CONCLUSION: The articular cartilage of rats was severely damaged in the model group, where obvious chondrocyte damage and disordered arrangement of chondrocytes were observed. The joint structure of the rats in the Cor I-H, Cor I-L and positive control groups tended to be normal, the chondrocytes were distributed uniformly, and the fissures were reduced. Compared with the model group, the relevant indicators in the Cor I-L and Cor I-H groups were significantly reduced, including the Mankin’s score of cartilage tissue, interleukin-1β, tumor necrosis factor α and matrix metalloproteinase-13 levels (P < 0.05), interleukin-6 and STAT3 immunoreactivities (P < 0.01) as well as the relative expression levels of p-JAK2 and p-STAT3 and ratios of p-JAK2/JAK2 and p-STAT3/STAT3 (P < 0.05). Compared with the positive control group, these indicators mentioned above were significantly increased in the Cor I-L group (P < 0.05); however, there was no significant difference between the positive control group and Cor I-H group. Results have confirmed that Cor I can delay knee osteoarthritis-induced cartilage tissue degeneration, and its mechanism may be related to reducing the were expression of inflammatory factors and inhibiting the inflammatory response mediated by interleukin-6/JAK2/STAT3 signaling pathway.

Key words: experiment, animal, rat, factor, protein, pathway, knee, osteoarthritis