Curcumin attenuates IL-1 β-induced chondrocyte damage by modulating the DUSP1/p38 MAPK pathway
Objective To investigate the inhibitory effect of curcumin(Cur)on IL-1 β-induced cartilage damage and to study the relationship between the regulatory mechanisms of the DUSP1/p38 MAPK signalling pathway in the above process.Methods Chondrocytes(C28/I2)and postoperative primary chondrocytes from osteoarthritis pa-tients were divided into control and experimental groups,and the experimental group was treated with different con-centrations of Cur(0,10,20,40,60,80 μmol/L)after applying the inflammatory induction treatment with IL-1 β(1 0 μg/L).The cell proliferation inhibition rate was determined by cell viability assay(CCK-8),the apoptosis rate was detected by flow cytometry assay.Real-time fluorescence quantitative PCR(qRT-PCR),Western blot,and immunofluorescence assay were used to detect type Ⅱ collagen α1 chain(Collagen Ⅱ),matrix metallopeptid-ase 13(MMP13),interleukin-1β(IL-1 β),BCL2-related X protein(Bax),B lymphocytoma-2(Bcl-2),dual-specificity phosphatase 1(DUSP1),p38 mitogen-activated protein kinase(p38),and phosphorylated p38 mito-gen-activated protein kinase(p-p38)RNA and protein expression levels.The role of the DUSP1/p38 MAPK axis in the inhibition of chondrocyte oxidative stress,apoptosis and inflammation by Cur was further validated using DUSP1 interfering RNA and p38 MAPK pathway inhibitor(SB).Results Cur significantly inhibited the IL-1 β-in-duced decrease in chondrocyte viability and significantly reduced the levels of oxidative stress,apoptosis,and in-flammation in chondrocytes;Cur inhibited the expression of MMP13,IL-1 β,Bax,and p-p38 proteins,while the expression of Collagen Ⅱ,Bcl-2,and DUSP1 proteins significantly increased;IL-1 β and interfering RNA silencing DUSP1 activated the p38 pathway,while Cur inhibited the activation of the p38 pathway;the use of p38 MAPK pathway inhibitors reduced cellular inflammation.Conclusion Cur attenuates IL-1 β-induced oxidative stress,ap-optosis and inflammation in chondrocytes by promoting the expression of DUSP1 protein and inhibiting the activation of p38 MAPK pathway.
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