AIM: The aim of the study was to identify osteoarthritis (OA)-related biological markers and processes. METHODS: The gene expression profile GSE46750 including 12 normal and 12 inflammatory synovial membrane samples, as well as the DNA methylation profile GSE43269, including 18 normal samples and 23 OA samples, were used. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were screened. Gene Ontology (GO) and pathway enrichment analysis together with protein-protein interaction (PPI) and microRNA (miRNA) regulatory networks of DEGs or DMGs were performed. Integrated analysis of DEGs and DMGs was conducted. RESULTS: A total of 662 DEGs, including 419 up- and 243 down-regulated genes as well as 198 DMGs, including 115 hypomethylated and 83 hypermethylated genes, were screened. GO terms and pathways enriched by up-regulated DEGs were mainly related to immune and inflammatory response. Down-regulated DEGs were entirely enriched in the cell cycle. Genes such as CDK1 (cyclin-dependent kinase 1) and MAD2L1 (MAD2 mitotic arrest deficient-like 1) were highlighted in PPI and the miRNA regulatory network. In addition, 14 overlapping genes between DEG and DMG lists, including CCL3L3 (chemokine C-C motif ligand 3) and IL-8 (interleukin 8) were obtained. Most of them were up-regulated and enriched in the immune and inflammatory response. CONCLUSION: Cell cycle and its related genes, including CDK1 and MAD2L1 (down-regulated), may contribute to the development of OA. Methylation, particularly hypomethylation of genes including IL-8 and CCL3L3 could make positive effects on OA progress. However, further studies are still needed to confirm our results.