Analysis and Verification of Potential Ferroptosis Key Genes in Curcumin Treatment of Osteoarthritis
Objective To explore the molecular mechanism of curcurin in the treatment of Osteoarthritic(OA)based on ferroptosis gene through bioinformatics.Methods Through Gene Expression Omnibus(GEO)retrieval,high-throughput sequencing data of curcumin in the treatment of osteoarthritis were downloaded.Principal component analysis was used to investigate the changes of principal components before and after curcumin treatment.limma algorithm was used to investigate the transcriptome changes before and after curcumin treatment.The change of signal pathway before and after curcumin treatment was investigated by gene ontology enrichment algorithm.GeneMANIA online tool was used to construct protein-protein interaction network and screen hub genes.The effect of curcumin therapy on hub gene expression was verified in vitro by fluorescence quantitative PCR.Results After curcumin treatment,the transcriptome expression and signaling pathway activity of chondrocytes were significantly changed(P＜0.05).Protein-protein interaction network showed that GCLC,HMOX1,FTL,FTH1 and SLC7A11 were ferroptosis hub genes.The results of ferrous ion fluorescence probe detection and intracellular Reactive oxygen species(ROS)detection showed that IL-1βsignificantly induced inflammation and increased the accumulation of Fe2+and ROS in chondrocytes compared with the control group.Curcumin treatment significantly alleviated IL-1(3-induced inflammation.The contents of Fe2+and ROS in chondrocytes were significantly decreased.The results of quantitative PCR and western blot showed that curcumin treatment significantly changed the expression level of hub gene(P＜0.05).Conclusion Curcumin may affect the ferroptosis process of chondrocytes by mediating up-regulation of GCLC and SLC7A11 genes and down-regulation of HMOX1,FTL and FTH1 genes,so as to have therapeutic effect on osteoarthritis.
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