Bioinformatics and system biology analysis revealed the crosstalk between COVID-19 and osteoarthritis
Bowen Lai1, Heng Jiang1, Taotao Liao1
1Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Insights
Bioinformatics identified four key genes common to COVID-19 and osteoarthritis (OA), offering potential diagnostic and therapeutic targets for both conditions. This research provides insights into shared pathologies and immune cell involvement.
Area of Science:
- Genomics and Bioinformatics
- Immunology
- Molecular Biology
Background:
- The COVID-19 pandemic has raised concerns about its impact on public health.
- An association between osteoarthritis (OA) and COVID-19 incidence/severity necessitates further investigation.
- Optimal diagnostic and treatment strategies for patients with co-occurring COVID-19 and OA are currently unclear.
Purpose of the Study:
- To explore the common pathological mechanisms between COVID-19 and osteoarthritis using bioinformatics.
- To identify potential diagnostic biomarkers and therapeutic targets for co-infected patients.
Main Methods:
- Screening of differentially expressed genes (DEGs) using the 'limma' R package.
- Construction of protein-protein interaction (PPI) networks and identification of hub genes via Cytoscape.
- Validation of hub genes in external datasets and an OA mouse model; prediction of regulatory microRNAs (miRNAs) and transcriptional factors (TFs); drug screening; and analysis of immune cell infiltration using CIBERSORT and scRNA-seq.
Main Results:
- Identified 74 common DEGs between COVID-19 and OA.
- Validated four hub genes (matrix metalloproteinases 9, ATF3, CCL4, RELA) as effective diagnostic markers for both diseases.
- Discovered 84 miRNAs and 28 TFs regulating hub gene expression, identified potential drugs (e.g., Simvastatin, Hydrocortisone), and observed distinct immune cell infiltration patterns (high Macrophage M0, low NK and Mast cells) in both conditions.
Conclusions:
- The identified hub genes, miRNAs, TFs, drugs, and immune infiltration patterns provide a deeper understanding of COVID-19 and OA pathogenesis.
- These findings suggest potential therapeutic targets for managing patients with both COVID-19 and osteoarthritis.
Background:
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.
Methods:
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.
Results:
A total of 74 common DEGs were identified between COVID-19 and OA. Receiver operating characteristic curves validated the effective diagnostic values (area under curve > 0.7) of four hub genes (matrix metalloproteinases 9, 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.
Conclusion:
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.
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