This study was carried out to explore the roles of circular RNAs (circRNAs) in nucleus pulposus (NP) tissues in intervertebral disc degeneration (IDD). Differentially expressed circRNAs in IDD and normal NP tissues were identified based on the results of microarray analysis. Bioinformatics techniques were employed to predict the direct interactions of selected circRNAs, microRNAs (miR), and mRNAs. CircRNA_104670 was selected as the target circRNA due to its large multiplier expression in IDD tissues. After luciferase reporter and EGFP/RFP reporter assays, we confirmed that circRNA_104670 directly bound to miR-17-3p, while MMP-2 was the direct target of miR-17-3p. The receiver-operating characteristic (ROC) curve showed that circRNA_104670 and miR-17-3p had good diagnostic significance for IDD (AUC circRNA_104670 = 0.96; AUC miRNA-17-3p = 0.91). A significant correlation was detected between the Pfirrmann grade and expression of circRNA_104670 ( r = 0.63; p = 0.00) and miR-17-3p ( r = −0.62; p = 0.00). Flow-cytometric analysis and the MTT assay showed that interfering with circRNA_104670 using small interfering RNA (siRNA) inhibited NP cell apoptosis ( p < 0.01), and this inhibition was reduced by interfering with miR-17-3p. Interfering with circRNA_104670 suppressed MMP-2 expression and increased extracellular matrix (ECM) formation, which were also reduced by interfering with miR-17-3p. Finally, an MRI evaluation showed that circRNA_104670 inhibition mice had a lower IDD grade compared with control mice ( p < 0.01), whereas circRNA_104670 and miRNA-17-3p inhibition mice had a higher IDD grade compared with circRNA_104670 inhibition mice ( p < 0.05). CircRNA_104670 is highly expressed in the NP tissues of IDD and acts as a ceRNA during NP degradation.
‘RNA sponges’ may provoke lower back pain by soaking up regulatory RNAs that normally protect the protein infrastructure surrounding cells in intervertebral discs. Many people suffer from lower back pain arising from disc degeneration (IDD). A team led by Fei-Zou and Jian-Yuan Jiang at Fudan University, Shanghai, China set out to identify molecular mechanisms that might contribute to IDD. They focused on circular RNAs, non-protein coding RNAs that have been linked to a variety of diseases. The researchers learned that IDD is associated with strongly elevated expression of a circular RNA that acts as an ‘RNA sponge’, binding to and thereby inactivating other RNA molecules. This inactivation ultimately results in the excessive production of an enzyme that can damage the protein matrix that supports cells within spinal discs, potentially setting up the conditions for IDD.