Exosome-Transported circRNA_0000253 Increase Intervertebral Disc Degeneration and Its Potential Mechanism

Abstract

Background: As society ages, intervertebral disc degeneration (IDD) causes great damage to humans. The pathogenesis of IDD is complex, and a better understanding of IDD pathogenesis at the molecular level may provide a better method for the treatment of IDD. Exosomes are 40-100 nm nano-sized vesicles that are released from many cell types into the extracellular space. We speculated that exosome-transported circular RNAs (circRNAs) could regulate IDD. Methods: Exosomes from samples of different degenerative grades were isolated and added to nucleus pulposus cells (NPCs), and indicators of NPC proliferation and apoptosis were detected. CircRNA microarray analysis was carried out, and the top 10 circRNAs were selected. PCR was performed to detect circRNA expression in normal and degenerated NPC exosomes, and the circRNA with the maximum upregulation was selected. Competing endogenous RNA (ceRNA) analysis was carried out. The function of the selected circRNA was verified in vivo and in vitro. Results: NPCs of different degenerative grades secreted exosomes, which could regulate IDD. CircRNA_0000253 was selected with the maximum upregulation in degenerative NPC exosomes. CeRNA analysis showed that circRNA_0000253 could adsorb microRNA-141-5p to up-regulate SIRT1. CircRNA_0000253 was also confirmed to increase IDD by competitively adsorbing microRNA-141-5p and up-regulating SIRT1 in vivo and in vitro. Conclusion: Exosomes secreted by NPCs could regulate IDD. CircRNA_0000253 was selected with the maximum upregulation in degenerative NPC exosomes and could promote IDD by competitively adsorbing microRNA-141-5p and down-regulating SIRT1. Funding Statement: Government funds were received in support of this work: National Natural Science Foundation of China (81972093, 81972109). Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: The study protocol was approved by Huashan Hospital Ethics Committee Affiliated with Fudan University. Informed consent was obtained from each donor. All animal procedures were approved by the Animal Care and Use Committee of Fudan University and were consistent with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.