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Osteoarthritis (OA) is one of the most common causes of disability and its development is associated with numerous factors. A major challenge in the treatment of OA is the lack of early diagnosis. In the present study, a bioinformatics method was employed to filter key genes that may be responsible for the pathogenesis of OA. From the Gene Expression Omnibus database, the datasets GSE55457, GSE12021 and GSE55325 were downloaded, which comprised 59 samples. Of these, 30 samples were from patients diagnosed with osteoarthritis and 29 were normal. Differentially expressed genes (DEGs) were obtained by downloading and analyzing the original data using bioinformatics. The Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways were analyzed using the Database for Annotation, Visualization and Integrated Discovery online database. Protein-protein interaction network analysis was performed using the Search Tool for the Retrieval of Interacting Genes/proteins online database. BSCL2 lipid droplet biogenesis associated, seipin, FOS-like 2, activator protein-1 transcription factor subunit (FOSL2), cyclin-dependent kinase inhibitor 1A (CDKN1A) and kinectin 1 (KTN1) genes were identified as key genes by using Cytoscape software. Functional enrichment revealed that the DEGs were mainly accumulated in the ErbB, MAPK and PI3K-Akt pathways. Reverse transcription-quantitative PCR analysis confirmed a significant reduction in the expression levels of FOSL2, CDKN1A and KTN1 in OA samples. These genes have the potential to become novel diagnostic and therapeutic targets for OA. [ABSTRACT FROM AUTHOR]