Effect of ginsenosides on the inflammatory response of mouse chondrocytes via Nrf2/HO-1 and NF-κB pathways
Objective:To investigate the therapeutic effects of ginsenoside Re(G-Re)on osteoarthritis(OA)and its molecular mechanisms.Methods:Mouse knee chondrocytes were cultivated in vitro and stimulated with IL-1β to simulate the pathological process of osteoarthritis.The cells were divided into the Control group(only added an equivalent amount of PBS),the IL-1β stimulation group,and the IL-1β+G-Re group(co-cultured with G-Re and IL-1β).Western blot technology and ELISA determination technology were employed to detect the expression changes of inflammation-related proteins,extracellular matrix synthesis-related proteins,and NF-κB signaling pathway-related proteins in different treatment groups.The expression changes of Nrf2 were detected by immunofluorescence staining technology.The siRNA technology was used to reduce the expression of Nrf2,and the expression changes of related proteins were detected by Western blot.A mouse osteoarthritis model(DMM model)was established and grouped for treatment.In the Control group,the joint capsule was opened without resecting the meniscus.In the DMM experimental group,the joint capsule was opened and the medial meniscus ligament was transected,dividing the medial meniscus into two parts.In the DMM+G-Re group,G-Re was intraperitoneally injected on the basis of the DMM group.After a period of time,the osteophytes and joint space of the mouse knee joints were detected by X-ray,and the therapeutic effect of G-Re in mice was evaluated by tissue immunofluorescence(IF).Results:In the chondrocytes treated with G-Re,the expression levels of inflammation-related proteins and NF-κB signaling pathway-related proteins were significantly reduced,while the expression levels of extracellular matrix synthesis-related proteins were significantly increased(P＜0.05).Compared with the control group,the expression levels of inflammation-related proteins in the G-Re treatment group were significantly decreased,and the expression levels of NF-κB signaling pathway-related proteins were also significantly reduced(P＜0.05).Compared with the Control group,the expression levels of extracellular matrix synthesis-related proteins in the G-Re treatment group were significantly increased,and the expression levels of ADAMTS5 and MMP13 were significantly down-regulated(P＜0.05).In the IL-1β+G-Re group compared with the IL-1β group,the nuclear transcription of Nrf2 protein was increased.After inhibiting the expression of Nrf2 in the si-Nrf2 group,the protein expressions of HO-1,COX-2,iNOS,p-p65/p65,etc.were increased compared with the IL-1β+G-Re group.Compared with the DMM group,the DMM+G-Re group alleviated the formation of osteophytes and the narrowing of the joint space.Conclusion:G-Re inhibits the inflammatory response of mouse chondrocytes and improves OA through the Nrf2/HO-l and NF-κB signaling pathways.
osteoarthritischondrocytesinflammationNrf2ginsenoside Re
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