CircCOG8 Downregulation Contributes to the Compression-Induced Intervertebral Disk Degeneration by Targeting miR-182-5p and FOXO3

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 downregulated 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.

Circ_0005918 Sponges miR-622 to Aggravate Intervertebral Disc Degeneration

“…For instance, demonstrated that circ_0040039 induced IDD progression by modulating the MiR-874-3p/ESR1 pathway axis. Xiang et al (2020) showed that downregulation of circCOG8 regulated the compression-induced IDD development by sponging the miR-182-5p/FOXO3 axis. In our study, by using Circular RNA Interactome software, we showed that circ_0005918 may sponge miR-622.…”

circPhc3 sponging microRNA‑93‑3p is involved in the regulation of chondrocyte function by mechanical instability in osteoarthritis

“…The chondrocytes in damaged cartilage are particularly susceptible to mechanical stress, and the tensile properties of damaged cartilage are lost due to the disrupted collagen network (22). Previous studies have found that the regulation of circRNAs by mechanical stress is involved in the pathogenesis of numerous diseases, such as intervertebral disk degeneration, orthodontic tooth movement and endplate cartilage degeneration (29)(30)(31). Xiang et al (30) reported that circcOG8 expression was obviously downregulated by mechanical stress in disk nucleus pulposus cells.…”

“…Previous studies have found that the regulation of circRNAs by mechanical stress is involved in the pathogenesis of numerous diseases, such as intervertebral disk degeneration, orthodontic tooth movement and endplate cartilage degeneration (29)(30)(31). Xiang et al (30) reported that circcOG8 expression was obviously downregulated by mechanical stress in disk nucleus pulposus cells. The circcOG8/miR-182-5p/FOXO3 pathway may also be considered an important underlying mechanism in the involvement of compression during the progression of intervertebral disc degeneration (30).…”

“…Xiang et al ( 30 ) reported that circCOG8 expression was obviously downregulated by mechanical stress in disk nucleus pulposus cells. The circCOG8/miR-182-5p/FOXO3 pathway may also be considered an important underlying mechanism in the involvement of compression during the progression of intervertebral disc degeneration ( 30 ). Xiao et al ( 32 ) detected tension-sensitive circRNA_0058097 molecules in human endplate chondrocytes, which might lead to novel preventative and therapeutic strategies for endplate cartilage degeneration.…”