Shuanghai DONG, Tian XİA, Lei WANG, Qinghua ZHAO, Jiwei TİAN

Investigation of candidate genes for osteoarthritis based on gene expression profiles

Objective: To explore the mechanism of osteoarthritis (OA) and provide valid biological information forfurther investigation.Methods: Gene expression probase. The Linear Models for Microarray Data (limma) package (Bioconductor project, http://www.bioconductor.org/packages/release/bioc/html/limma.html) was used to identify differentially expressedgenes (DEGs) in inﬂamed OA samples. Gene Ontology function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were performed basedon Database for Annotation, Visualization and Integrated Discovery data, and proteineprotein interaction(PPI) network was constructed based on the Search Tool for the Retrieval of Interacting Genes/Proteinsdatabase. Regulatory network was screened based on Encyclopedia of DNA Elements. Molecular ComplexDetection was used for sub-network screening. Two sub-networks with highest node degree were integrated with transcriptional regulatory network and KEGG functional enrichment analysis was processed for 2 modules.Results: In total, 401 up- and 196 down-regulated DEGs were obtained. Up-regulated DEGs wereinvolved in inﬂammatory response, while down-regulated DEGs were involved in cell cycle. PPI networkwith 2392 protein interactions was constructed. Moreover, 10 genes including Interleukin 6 (IL6) andAurora B kinase (AURKB) were found to be outstanding in PPI network. There are 214 up- and 8 downregulated transcription factor (TF)-target pairs in the TF regulatory network. Module 1 had TFs includingSPI1, PRDM1, and FOS, while module 2 contained FOSL1. The nodes in module 1 were enriched inchemokine signaling pathway, while the nodes in module 2 were mainly enriched in cell cycle.Conclusion: The screened DEGs including IL6, AGT, and AURKB might be potential biomarkers for genetherapy for OA by being regulated by TFs such as FOS and SPI1, and participating in the cell cycle andcytokineecytokine receptor interaction pathway.

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