Identification Of Potential Target Genes In Osteoarthritis By Weight Gene Co-expression Network Analysis

Osteoarthritis is the most common arthritis in the world,while pathophysiology of osteoarthritis is not fully understood.The existing treatment strategies mainly include pain relief treatment,exercise therapy and surgical therapy,but no tar medicine yet.Based on the above problems,we intent to mine potential target genes in osteoarthritis by construte weighted gene coexpress network based on microarray data sets to provide novel evidence for target of new drug in future.ObjectiveArticular cartilage and chondrocytes play a key role in the development of knee osteoarthritis while the molecular mechanisms of cartilage degeneration have not been fully explored.The present study was undertaken to discriminate potential target genes from gene interaction network in the knee cartilage of osteoarthritis(OA)patients by WGCNA.MethodsHere,we downloaded the mRNA profiles of GSE66635 and GSE98460 including 12 health cartilage and 46 osteoarthritis cartilage from Gene Expression Omnibus(GEO)database.Weighted gene co-expression network analysis(WGCNA)were applied to screen potential OA-related genes.To reveal the functions or pathways of OA-related genes,we use the ClusterProfiler package of R software to perform Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Hub-genes were distinguished by MCC algorism in Cytoscape software and verified in primary murine cartilage by qPCR.ResultsIn this study,we divided 23 modules from WGCNA and identified 10 hub-genes by cytoscape software,wh ich subsequently verified 7 hub-genes in primary chondrocytes.Conclusionwe provided evidence that LRRK2,TRIM25,EZH1,RBMS3 and OLFML1 were downregulated in OA chondrocytes,which might contribute to further therapeutic research of osteoarthritis.