Bioinformatics and system biology analysis revealed the crosstalk between COVID-19 and osteoarthritis.

Abstract

The global coronavirus disease 2019 (COVID-19) outbreak has significantly impacted public health. Moreover, there has been an association between the incidence and severity of osteoarthritis (OA) and the onset of COVID-19. However, the optimal diagnosis and treatment strategies for patients with both diseases remain uncertain. Bioinformatics is a novel approach that may help find the common pathology between COVID-19 and OA. Differentially expressed genes (DEGs) were screened by R package "limma."Functional enrichment analyses were performed to find key biological functions. Protein-protein interaction (PPI)network was constructed by STRING database and then Cytoscape was used to select hub genes. External data sets and OA mouse model validated and identified the hub genes in both mRNA and protein levels. Related transcriptional factors (TF) and microRNAs (miRNAs) were predicted with miRTarBase and JASPR database. Candidate drugs were obtained from Drug Signatures database. The immune infiltration levels of COVID-19 and OA were evaluated by CIBERSORT and scRNA-seq. A total of 74 common DEGs were identified between COVID-19 and OA. Receiver operating characteristiccurves validated the effective diagnostic values (area under curve > 0.7) of four hub genes (matrix metalloproteinases9, ATF3, CCL4, and RELA) in both the training and validation data sets of COVID-19 and OA. Quantitative polymerase chain reaction and Western Blot showed significantly higher hub gene expression in OA mice than in healthy controls. A total of 84 miRNAs and 28 TFs were identified to regulate the process of hub gene expression. The top 10 potential drugs were screened including "Simvastatin,""Hydrocortisone,"and "Troglitazone" which have been proven by Food and Drug Administration. Correlated with hub gene expression, Macrophage M0 was highly expressed while Natural killer cells and Mast cells were low in both COVID-19 and OA. Four hub genes, disease-related miRNAs, TFs, drugs, and immune infiltration help to understand the pathogenesis and perform further studies, providing a potential therapy target for COVID-19 and OA.