Abstract
Circular RNAs (circRNAs) have been increasingly demonstrated to play critical roles in the pathogenesis of various human diseases. Intervertebral disk degeneration (IDD) is recognized as the major contributor to lower back pain, and mechanical stress is a predominant trigger for IDD. However, little is known about the part that circRNAs play in the involvement of mechanical stress during IDD development. In the present study, we identified a novel circRNA and examined the role of this circRNA in a compression loading-induced IDD process. We detected the expression pattern of circCOG8 and observed its function in disk NP cells under mechanical stress. We conducted bioinformatics analysis, RNA immunoprecipitation experiment, and reporter gene assay to unveil the mechanism of the circCOG8 downregulation mediated IVD degeneration. Results showed that the circCOG8 expression was obviously down-regulated by the mechanical stress in disk NP cells. CircCOG8 attenuated NP cells apoptosis, intracellular ROS accumulation, and ECM degradation in vitro and ex vivo. CircCOG8 directly interacted with miR-182-5p and, thus, modulated the FOXO3 expression to affect the compression-induced IDD progression. Altogether, the present study revealed that the circCOG8/miR-182-5p/FOXO3 pathway was an important underlying mechanism in the involvement of compression during the IDD progression. Intervention of circCOG8 is a new therapeutic strategy for IDD treatment.
Highlights
Lower back pain is a global health problem with a high morbidity and it is the leading cause of job disability in the modern society (Hoy et al, 2014)
To uncover the potential role of circRNAs in the progression of intervertebral disk degeneration (IDD) induced by mechanical loading, we examined the effects of compression on human disk nucleus pulposus (NP) cells in three different samples
Previous studies have demonstrated that intervertebral disk (IVD) degeneration was a complicated disease involving numerous pathologic processes during which the nucleus pulposus cells residing in the IVD center has played a key role (Sakai et al, 2012)
Summary
Lower back pain is a global health problem with a high morbidity and it is the leading cause of job disability in the modern society (Hoy et al, 2014). There are various initiating contributors associated with lower back pain, it is widely accepted that the intervertebral disk degeneration (IDD) is the major reason (Hughes et al, 2012). The abundance of ECM, including the proteoglycans and type II collagen generated by the NP cells, make important contributions to the physiological structure and function of IVD (Roughley, 2004). IVD degeneration is typically characterized by the aberrant conditions of NP cells that the ECM catabolism exceeds anabolism, cell apoptosis rates are abnormally increased, and reactive oxygen species (ROS) generation and antioxidant defense get out of balance to cause oxidative stress (Zhao et al, 2007; Risbud and Shapiro, 2014; Feng et al, 2017). Deep research into the underlying mechanism of these aberrant activities of the NP cells can help clinicians get a better understanding of the IDD pathogenesis and, provide new strategies for the IDD treatment (Hughes et al, 2012; Sakai and Grad, 2015)
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