The molecular link between obstructive sleep apnea and osteoarthritis: based on bioinformatics analysis and experimental validation.

ABSTRACT

BACKGROUND: Obstructive sleep apnea (OSA) and osteoarthritis (OA) are highly prevalent and seriously affect the patient's quality of life. Patients with OSA have a high incidence of OA, however, the underlying mechanism remains unclear. Here, we investigated the molecular link between OSA and OA via bioinformatics analysis and experimental validation. METHODS: We downloaded a peripheral blood monocyte microarray profile (GSE75097) for patients with OSA and two synovial microarray profiles (GSE55235 and GSE55457) for patients with OA from the Gene Expression Omnibus database. We identified OSA-associated differentially expressed genes (OSA-DEGs) in patients with OA. Additionally, we constructed protein-protein interaction networks to identify the key genes involved in OA. Immunohistochemistry was performed to verify the expression of key genes in OA rat models. RNA interference assay was performed to validate the effects of key genes on synovial cells. Gene-miRNA, gene-transcription factor, and gene-drug networks were constructed to predict the regulatory molecules and drugs for OA. RESULTS: Fifteen OSA-DEGs screened using the threshold criteria were enriched in the tumor necrosis factor (TNF) pathway. Combining the 12 algorithms of CytoHubba, we identified JUNB, JUN, dual specificity phosphatase 1 (DUSP1), and TNF-alpha-induced protein 3 (TNFAIP3) as the key OSA-DEGs involved in OA development. Immunohistochemistry and quantitative polymerase chain reaction revealed that these key genes were downregulated in the OA synovium, promoting TNF-α expression. Therefore, OSA-DEGs, JUN, JUNB, DUSP1, and TNFAIP3 function in OA by increasing TNF-α expression. Our findings provide insights on the mechanisms underlying the effects of OSA on OA.