Several researchers have focused on understanding the pathogenesis and treatment strategies for osteoarthritis (OA). Gastrodin (GAS) is a potential anti-inflammatory agent. In this study, we constructed an in vitro OA chondrocyte model by treating chondrocytes with IL-1β. Next, we determined the expression of aging-related markers and mitochondrial functions in chondrocytes treated with GAS. Further, we constructed a "drug-component-target-pathway-disease" interactive network and determined the effect of GAS on the functions and pathways related to OA. Finally, we constructed the OA rat model by removing the medial meniscus of the right knee and transection of the anterior cruciate ligament. The results revealed that GAS reduced senescence and improved mitochondrial functions in OA chondrocytes. We used network pharmacology and bioinformatics to screen for key molecules Sirt3 and the PI3K-AKT pathway involved in regulating the effect of GAS on OA. Further studies showed an increase in SIRT3 expression and reduced chondrocyte aging, mitochondrial damage, and the phosphorylation of the PI3K-AKT pathway. The results showed that GAS ameliorates pathological changes related to aging, increases SIRT3 expression, and protects the ECM in the OA rat model. These results were consistent with our bioinformatics results and previous studies. In summary, GAS slows down the aging of chondrocytes and mitochondrial damage in OA by regulating the phosphorylation of the PI3K-AKT pathway via SIRT3.
Keywords: Cell senescence; Chondrocytes; Gastrodin; Mitochondrial function; Network pharmacology; Osteoarthritis.
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