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

Yanbin Fu,Letian Shan,Li Zhou,Peijian Tong,Haipeng Xu,Xiujuan Xiao,Yanzhi Ge,Zuxiang Chen

doi:10.1186/s41065-021-00201-0

Abstract

BackgroundOsteoarthritis (OA) and rheumatoid arthritis (RA) were two major joint diseases with similar clinical phenotypes. This study aimed to determine the mechanistic similarities and differences between OA and RA by integrated analysis of multiple gene expression data sets.MethodsMicroarray data sets of OA and RA were obtained from the Gene Expression Omnibus (GEO). By integrating multiple gene data sets, specific differentially expressed genes (DEGs) were identified. The Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and protein–protein interaction (PPI) network analysis of DEGs were conducted to determine hub genes and pathways. The “Cell Type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT)” algorithm was employed to evaluate the immune infiltration cells (IICs) profiles in OA and RA. Moreover, mouse models of RA and OA were established, and selected hub genes were verified in synovial tissues with quantitative polymerase chain reaction (qPCR).ResultsA total of 1116 DEGs were identified between OA and RA. GO functional enrichment analysis showed that DEGs were enriched in regulation of cell morphogenesis involved in differentiation, positive regulation of neuron differentiation, nuclear speck, RNA polymerase II transcription factor complex, protein serine/threonine kinase activity and proximal promoter sequence-specific DNA binding. KEGG pathway analysis showed that DEGs were enriched in EGFR tyrosine kinase inhibitor resistance, ubiquitin mediated proteolysis, FoxO signaling pathway and TGF-beta signaling pathway. Immune cell infiltration analysis identified 9 IICs with significantly different distributions between OA and RA samples. qPCR results showed that the expression levels of the hub genes (RPS6, RPS14, RPS25, RPL11, RPL27, SNRPE, EEF2 and RPL19) were significantly increased in OA samples compared to their counterparts in RA samples (P < 0.05).ConclusionThis large-scale gene analyses provided new insights for disease-associated genes, molecular mechanisms as well as IICs profiles in OA and RA, which may offer a new direction for distinguishing diagnosis and treatment between OA and RA.

Highlights

Osteoarthritis (OA) and rheumatoid arthritis (RA) were two major joint diseases with similar clinical phenotypes
Gene Ontology (GO) pathway of OA‐specific and RA‐specific differentially expressed genes (DEGs) GO annotations analysis showed that OA-specific DEGs (Table 5, Fig. 4A) were predominantly enriched in regulation of neuron projection development, regulation of cell morphogenesis involved in differentiation, and positive regulation of neuron differentiation; nuclear speck, RNA polymerase II transcription factor complex, and adherens junction; protein serine/ threonine kinase activity, proximal promoter sequencespecific DNA binding, and RNA polymerase II proximal promoter sequence-specific DNA binding
RAspecific DEGs (Table 5, Fig. 4B) were primarily enriched in cell morphogenesis involved in neuron differentiation, regulation of cell morphogenesis involved in differentiation, and positive regulation of neuron differentiation; nuclear speck, RNA polymerase II transcription factor complex, and transcription factor complex; protein serine/threonine kinase activity, SMAD binding, Table 2 Primer sequences of target genes

Summary

Introduction

Osteoarthritis (OA) and rheumatoid arthritis (RA) were two major joint diseases with similar clinical phenotypes. Rheumatoid arthritis (RA) is one of the most common autoimmune diseases among connective tissue disorders, which typically involves small joints such as hands and feet [2]. Similar to OA, RA reduces quality of life and increases the risk of disability in affected patients, and imposes considerable financial and societal burdens on healthcare systems worldwide [3]. Both OA and RA patients have comparable symptoms, including pain, swelling, and dysfunction around the joints [4]. The specific diagnosis of OA and RA remains restricted due to their unclear pathological mechanisms

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