Xiang Shuai, Li Zeng, Bian Yanyan, Weng Xisheng
Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China.
J Cell Biochem. 2019 Oct;120(10):18031-18040. doi: 10.1002/jcb.29106. Epub 2019 Jun 12.
The role of circular RNAs (circRNAs) in regulating cartilage homeostasis in osteoarthritis (OA) has been reported. However, the regulatory mechanisms of circRNAs in OA synovium remains basically unidentified. The current study intended to divulge the expression profile of circRNAs in OA synovium and investigate the possible molecular mechanisms of circRNAs in synovitis in OA through an integrated bioinformatics analysis. A total of 35 synovium samples were collected, including 17 from patients with knee OA and 18 from controls. circRNA sequencing was then carried out on five OA synovium samples as well as five controls to explore the expression pattern of the circRNAs. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was done to confirm the manifestation levels of six differentially expressed circRNAs. Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were done for differentially expressed circRNAs using the DAVID database to annotate the functions. The circRNA-miRNA coexpression network was then created to estimate the probable molecular regulatory mechanisms of specifically expressed circRNAs in OA synovium. Total of 122 circRNAs were found to be differentially expressed in OA synovium through RNA sequencing. The expressions of five downregulated circRNAs as well as an upregulated circRNA were confirmed through the use of qRT-PCR. The circRNA-miRNA network was created to annotate the probable molecular regulatory mechanisms of specifically expressed circRNAs. Our outcomes revealed that circRNAs might be incorporated in the initiation as well as development of OA synovitis and might have prospective importance in OA diagnosis and therapy.
环状RNA(circRNAs)在骨关节炎(OA)中调节软骨稳态的作用已有报道。然而,circRNAs在OA滑膜中的调控机制基本仍未明确。本研究旨在通过综合生物信息学分析揭示circRNAs在OA滑膜中的表达谱,并探讨circRNAs在OA滑膜炎中的可能分子机制。共收集了35份滑膜样本,其中17份来自膝骨关节炎患者,18份来自对照组。然后对5份OA滑膜样本和5份对照样本进行circRNA测序,以探索circRNAs的表达模式。采用实时定量逆转录-聚合酶链反应(qRT-PCR)来确认6种差异表达circRNAs的表达水平。使用DAVID数据库对差异表达的circRNAs进行基因本体论(GO)以及京都基因与基因组百科全书通路(KEGG)富集分析,以注释其功能。随后构建circRNA-miRNA共表达网络,以评估OA滑膜中特异性表达的circRNAs可能的分子调控机制。通过RNA测序发现共有122种circRNAs在OA滑膜中差异表达。通过qRT-PCR证实了5种下调的circRNAs以及1种上调的circRNA的表达。构建circRNA-miRNA网络以注释特异性表达的circRNAs可能的分子调控机制。我们的结果表明,circRNAs可能参与了OA滑膜炎的发生和发展,并且可能在OA的诊断和治疗中具有潜在重要性。