Ren Xun-Shan, Xie Ting, Zhuang Huang-Ming, Lei Tian-Run, Jiang Fu-Ze, Zhou Pang-Hu
Department of Orthopedics, Renmin Hospital of Wuhan University Wuhan, Hubei, China.
Department of Women's Health Care, Maternal and Child Health Hospital of Hubei Province Wuhan, Hubei, China.
Am J Transl Res. 2023 Jul 15;15(7):4487-4503. eCollection 2023.
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.
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.
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.
阻塞性睡眠呼吸暂停（OSA）和骨关节炎（OA）非常普遍，严重影响患者的生活质量。OSA患者的OA发病率很高，但其潜在机制仍不清楚。在此，我们通过生物信息学分析和实验验证研究了OSA与OA之间的分子联系。
我们从基因表达综合数据库下载了OSA患者的外周血单核细胞微阵列谱（GSE75097）以及OA患者的两个滑膜微阵列谱（GSE55235和GSE55457）。我们鉴定了OA患者中与OSA相关的差异表达基因（OSA-DEGs）。此外，我们构建了蛋白质-蛋白质相互作用网络以识别参与OA的关键基因。进行免疫组织化学以验证OA大鼠模型中关键基因的表达。进行RNA干扰试验以验证关键基因对滑膜细胞的影响。构建基因- miRNA、基因-转录因子和基因-药物网络以预测OA的调控分子和药物。
使用阈值标准筛选出的15个OSA-DEGs在肿瘤坏死因子（TNF）通路中富集。结合CytoHubba的12种算法，我们确定JUNB、JUN、双特异性磷酸酶1（DUSP1）和TNF-α诱导蛋白3（TNFAIP3）是参与OA发展的关键OSA-DEGs。免疫组织化学和定量聚合酶链反应显示，这些关键基因在OA滑膜中下调，促进TNF-α表达。因此，OSA-DEGs、JUN、JUNB、DUSP1和TNFAIP3通过增加TNF-α表达在OA中发挥作用。我们的研究结果为OSA对OA影响的潜在机制提供了见解。
