Osthole attenuates cartilage degradation and chondrocyte pyroptosis in knee osteoarthritis and is associated with activation of the PI3K/Akt pathway.

OBJECTIVE

To verify the protective effect of osthole on knee osteoarthritis (KOA) and explore its mechanism of action.

METHODS

Rats receiving the modified Hulth method and IL-1β-induced chondrocytes were used to construct in vivo and in vitro KOA models, respectively, and were subsequently treated by osthole. Hematoxylin-eosin and safranin O/fast green staining assays were used to assess the histological effects of osthole administered by oral gavage on the knee joint cartilage of KOA model rats. Western blotting, qRT-PCR, and immunofluorescence and immunohistochemical staining analyses were used to examine the expression of factors related to cartilage degeneration and chondrocyte pyroptosis in vitro and in vivo. The potential molecular targets of osthole action on KOA and their relevant pathways were predicted and verified.

RESULTS

Osthole alleviated cartilage injury and lowered pathology scores in KOA rats. Osthole increased the levels of collagen Ⅱ but decreased those of ADAMTS-5, MMP3, and MMP13 in rat chondrocytes. Chondrocyte pyroptosis was alleviated by osthole, as evidenced by decreased levels of NLRP3, caspase-1, ASC, GSDMD, IL-1β, and IL-18 in rat chondrocytes and serum. Osthole prevented LDH release in rat chondrocytes induced by IL-1β. Bioinformatics analysis showed that osthole targets the PI3K/Akt pathway. PI3K inhibitor LY294002 treatment reversed the effects of osthole on chondrocyte degeneration and pyroptosis.

CONCLUSION

Osthole alleviated cartilage degradation and chondrocyte pyroptosis in KOA, and these effects were associated with activation of the PI3K/Akt signaling pathway.