Identification and validation of hub genes of synovial tissue for patients with osteoarthritis and rheumatoid arthritis

Abstract

Osteoarthritis (OA) and rheumatoid arthritis (RA) were two major joint diseases with partially common phenotypes and genotypes. This study aimed to determine the mechanistic similarities and differences between osteoarthritis and rheumatoid arthritis by analyzing the differentially expressed genes and signaling pathways. Microarray data of osteoarthritis and rheumatoid arthritis were obtained from the Gene Expression Omnibus. By integrating multiple gene data sets, specific differentially expressed genes (DEGs) were identified in synovial membrane samples from patients and healthy donations. Then, the Gene ontology significant functions annotation, Kyoto Encyclopedia of Genes and Genomes pathways and protein-protein interaction network analysis were conducted. Moreover, CIBERSORT was used to further distinguish OA and RA in immune infiltration. Finally, animal experimentation was conducted and the establishment of model, which was verified using PCR in the mouse. As an overlapping process, we identified 1116 DEGs between OA and RA. It was indicated that specific gene signatures differed significantly between OA and RA connected with the distinct pathways. Of identified DEGs, 9 immune cell types among 22 were identified to distinguish from each other. The qRT-PCR result showed that the eight-tenths expression levels of the hub genes were significantly increased in OA samples (P < 0.05). This large-scale gene expression study provided new insights for disease-associated genes and molecular mechanisms as well as their associated function in osteoarthritis and rheumatoid arthritis, which simultaneously offer a new direction for biomarker development and the distinguishment of gene-level mechanisms between osteoarthritis and rheumatoid arthritis.