关键词: 橙皮素, 骨髓间充质干细胞, 成软骨分化, 软骨细胞, 骨关节炎

Abstract: Objective To evaluate the effect of hesperetin (HST) on cartilage damage in mouse models of destabilization in medial meniscus (DMM)-induced osteoarthritis, and to explore mechanisms. Methods 1)In vitro experiments: 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 inflammation-related genes. 2) Animal experiments:A mouse DMM model of osteoarthritis was established, and hesperetin was administered by intra-articular injection. Gait analysis, histological staining, and Osteoarthritis Research Society 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 reduced 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 mRNA 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 inflammatory stimulation.

Key words: hesperetin, bone marrow mesenchymal stem cell, chondrogenic differentiation, chondrocyte, osteoarthritis