| Background: Knee osteoarthritis(OA)is a complex and common chronic disease,which has a high incidence and disability rate in the elderly.The degeneration of articular cartilage plays an important role in the progress of OA.Cell death is the basic physiological process of all organisms,which plays an important role in maintaining body balance and preventing the development of diseases.At present,the mechanism of chondrocyte death has not been fully clarified.As a new cell death mechanism,ferroptosis may participate in the process of osteoarthritis.In this study,we screened and verified the genes related to ferroptosis in OA through bioinformatics methods.Objective: to screen and verify ferroptosis related genes in OA by mechanical learning.Methods:(1)downloading the gene expression data of normal and knee OA cartilage from GEO database,screening ferroptosis rela ted genes by bioinformatics method,KEGG and GO enrichment analysis,(2)screening and selecting intersection of ferroptosis related genes in OA based on two mechanical learning algorithms(lasso regression algorithm and SVM-RFE algorithm),and then predic ting key genes according to the protein interaction of screened genes.(3)the expression differences of key genes were analyzed in the verification set,and the diagnostic accuracy of key genes was analyzed by receiver working characteristic curve(ROC).Finally,the expression of ARNTL was verified in OA model rats.Results:(1)58 differentially expressed ferroptosis related genes were screened from knee OA cartilage by bioinformatics analysis.Pathway and functional enrichment analysis showed that these genes were mainly involved in ferroptosis,osteoclast and adipocyte differentiation and HIF-1signal pathway.(2)based on lasso regression algorithm and SVM-RFE algorithm,13 and 12 central genes were screened for ferroptosis related genes in OA,respectively,and 6 central genes were selected according to protein interaction.(3)the differential expression level of hub gene and the receiver working characteristic curve(ROC)were verified in two verification sets,and it was predicted that ARNTL might be involved in the process of iron death of OA chondrocytes,and then affected the process of ferroptosis.(4)in SD rats with knee OA induced by sodium iodoacetate,the expression of ARNTL was low and GPX4 was low.Conclusion: in this study,we screened the genes related to ferroptosis in OA,and identified ARNTL as the key gene through mechanical learning,training set and verification set.ARNTL was low expressed in OA chondrocytes,and the difference was also observed in OA rats,indicating that ARNTL may be a potential regulatory target of ferroptosis in OA chondrocytes.The purpose of this study is to provide reference for further study on the mechanism of ferroptosis in OA chondrocytes. |
