Screening And Identification Of Key Genes In Osteoarthritis

Objective As one of the most common orthopedic diseases,osteoarthritis has been threatening people's health for a long time.With the development of aging society,this problem is more serious.However,the etiology and molecular mechanism of osteoarthritis have not been elucidated.In the past,the research on cartilage lesions in the pathogenesis of osteoarthritis was the most extensive,but the research on the pathogenesis of synovium and subchondral bone was few.In this study,bioinformatics technology was used to explore the molecular mechanism of osteoarthritis.Methods GSE82107 and GSE51588 of Osteoarthritis Synovium and subchondral bone were downloaded from GEO database.GEO2 R was used to screen the DEGs of the two groups.P < 0.05 and | logfc | > 1 were used as the screening conditions.After that,GO analysis and KEGG analysis were carried out on the website of metascape to enrich and annotate the DEGs.Then we use STRING online tool analysis to analyze the DEGs,and construct the PPI network based on the DEGs,with the confidence score > 0.4.Then we input the PPI interaction results from STRING analysis into Cytoscape for visualization,and we use the MCODE plug-in to detect the closely connected module areas in the PPI network.The parameters are set as follows: mcode scores > 5,degree cut-off = 2,node score cut-off = 0.2,max depth = 100 and k-score = 2.According to the principle of degree > 10,we used Cytohubba to screen hub genes and annotate the expression and regulation of these genes.Betwweennes and bottleneck are used as complementary indicators of degree to identify the date hub gene in the network.Finally,the first 10 genes with degree > 20 were used as key genes to investigate the tissue specificity of gene expression with GTEX database.Results Using GEO2 R to analyze the data,3805 DEGs were screened out in GSE82107,including 689 up-regulated genes and 3116 down-regulated genes;2298 differential genes were screened out in GSE51588,including 1390 up-regulated genes,908 down regulated genes,and 355 genes were obtained by overlapping the two data sets.The results of GO analysis and KEGG analysis showed that the DEGs were mainly enriched in the biological processes and pathways of NABA CORE MATRISOME,ossification,connective tissue development and developmental growth.We analyzed the functions of the key modules identified by MCODE with metascape,and found that they were mainly enriched in NABA CORE MATRISOME,Alcoholism and G?(i)signalling events.By using the cytohubba plug-in of Cytoscape,38 hub genes with degree > 10 were obtained,including 17 up-regulated genes,15 down regulated genes,and 6 genes with different regulatory directions in the two groups.The top 10 genes with degree >18 were selected as key genes,of which FN1 was the most significant.GTEX database showed that the expression of FN1,MMP2,RUNX2,LUM,COL1A1,COL6A2 in transformed fibroblasts had high tissue specificity.Conclusion The purpose of this study is to provide a more comprehensive perspective to understand osteoarthritis,to screen the DEGs of synovium and subchondral bone,and to identify the function of key modules and some hub genes,which may be a new entry point for the study of osteoarthritis.But these are still data level predictions,which still need to be verified by a large number of experiments.