橙皮素减轻骨关节炎模型小鼠软骨损伤OA

Objective To evaluate the effect of hesperetin(HST)on cartilage damage in mouse models of destabi-lization in medial meniscus(DMM)-induced osteoarthritis,and to explore mechanisms.Methods 1)In vitro exper-iments:CCK-8 assay was used to evaluate the effect of hesperetin on bone marrow mesenchymal stem cells(BM-MSCs)viability.BM-MSCs chondrogenic induction model was established and chondrogenic differentiation was evaluated by type Ⅱ collagen(COL2)immunofluorescence staining microscopy;An IL-1β-induced chondrocyte inflammatory model was established,and real-time quantitative PCR was used to detect the expression of inflam-mation-related genes.2)Animal experiments:A mouse DMM model of osteoarthritis was established,and hespere-tin was administered by intra-articular injection.Gait analysis,histological staining,and Osteoarthritis Research So-ciety International(OARSI)scoring were used to evaluate its effects.Results Within the concentration range of 0.4-10 μmol/L,hesperetin had no significant effect on BM-MSCs viability,whereas 50 μmol/L hesperetin re-duced BM-MSCs viability(P＜0.05).Compared to the control group,hesperetin enhanced COL2 expression during BM-MSCs chondrogenic induction(P＜0.05).In IL-1β-stimulated chondrocytes,hesperetin downregulated the mR-NA expression levels of IL-1β,IL-6,and TNF-α(P＜0.05).In the DMM mouse model,hesperetin improved gait abnormalities,alleviated cartilage damage and reduced OARSI scores(P＜0.05).Conclusions In osteoarthritis of DMM mouse models,hesperetin alleviated cartilage damage.Its effects may be associated with the promotion of BM-MSCs chondrogenic differentiation and inhibition of inflammation-related gene expression in chondrocytes under in-flammatory stimulation.