Abstract：Objective: To investigate the mechanism of hyperoside (HYP) on cartilage tissue damage in knee osteoarthritis (KOA) rats based on Hippo/YAP pathway. Methods: Based on the improved Hulth method, a KOA rat model was constructed. KOA rats were assigned to the model group, the low-dose HYP group (HYP-L, 25 mg/kg HYP), the high-dose HYP group (HYP-H, 50 mg/kg HYP), and the high-dose HYP+VTFP group (YAP inhibitor) (HYP-H+VTFP, 50 mg/kg HYP, 10 mg/kg VTFP), each with 12 rats. Another 12 rats with exposed joint cavities without any other treatment were set as the sham surgery group (sham group). Lequesne MG was used to evaluate rat behavior. ELISA was used to detect TNF-α, IL-1β, IL-6, MMP-3, and MMP-13 in joint fluid. HE and safranin O-green staining were used to observe the pathological condition of cartilage tissue. TUNEL method was used to detect chondrocyte apoptosis. In addition, Western blot was used to detect TAZ and YAP proteins. Results: For the sham group, the model group showed manifest increases in rat behavioral scores, TNF-α, IL-1β, IL-6, MMP-3, and MMP-13, and chondrocyte apoptosis rate, and obvious decreases in TAZ and YAP (P<0.05), the results of HE staining and safranin O-green staining showed severe cartilage tissue defects, reduced cell numbers, rough surface, and disordered staining distribution. For the model group, the HYP-L and HYP-H groups showed manifest reductions in rat behavioral scores, TNF-α, IL-1β, IL-6, MMP-3, and MMP-13, and chondrocyte apoptosis rate, and obvious increases in TAZ and YAP (P<0.05), the thickness and number of cells in cartilage tissue increased, and surface damage was reduced. VTFP could, to some extent, reduce the improvement effect of HYP on cartilage tissue damage in KOA rats. Conclusion: HYP may alleviate cartilage tissue damage in KOA rats by adjusting Hippo/YAP pathway.
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2025, Vol. 31 
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