The pathological mechanisms of circRNAs in mediating intervertebral disc degeneration

Abstract

Lower back pain (LBP) is a worldwide health problem associated with significant economic and social burden. Intervertebral disc degeneration (IVDD) is a leading cause of LBP. Several studies show that the death of nucleus pulposus cells (NPCs), abnormal metabolism of the extracellular matrix (ECM), and inflammatory response are the key mechanisms behind the pathogenesis of IVDD. Circular RNAs (circRNAs) are key regulators of gene expression and play a significant role in regulating NPCs death, ECM homeostasis, and inflammatory response by acting as microRNAs (miRNAs) sponges in IVDD. However, the regulatory role of circRNAs in mediating IVDD remains unknown. This review comprehensively describes the normal anatomic structure and function of IVD, the pathogenesis of IVDD, the characteristics, synthesis, mechanisms, and function of circRNAs. Moreover, we highlighted the 23 circRNAs that mediate ECM metabolism, 16 circRNAs that mediate NPCs apoptosis, circ_0004354 and circ_0040039 that mediate NPCs pyroptosis, and 5 circRNAs that mediate inflammatory response in IVDD. In addition, this review presents suggestions for future studies, such as the need for further investigation on ferroptosis-related circRNAs in IVDD. This review could provide novel insights into the pathogenesis and treatment of IVDD.

Keywords: Circular RNAs; Extracellular matrix; Inflammatory response; Intervertebral disc degeneration; Nucleus pulposus cells.

Fig. 1

The pathological process of IVDD. (A) Secretion of proinflammatory factor by nucleus pulposus cells; (B) Apoptosis of nucleus pulposus cells and inflammatory response; (C) ECM degradation caused by MMPs.

Fig. 2

Different circRNAs act as protector or inhibitor in IVDD by regulating ECM metabolism, apoptosis, pyroptosis, and inflammatory response. In the upper half of the ellipse, 10 circRNAs promote ECM degradation; 9 circRNAs promote cells apoptosis; 2 circRNAs promote cells pyroptosis; 4 circRNAs promote inflammatory response; thus, these IVDD-related circRNAs were regarded as IVDD-inhibitor. In the lower half of the ellipse, 12 circRNAs promote ECM synthesis; 7 circRNAs inhibit cells apoptosis; 2 circRNAs inhibit inflammatory response; thus, these IVDD-related circRNAs were regarded as IVDD-protector.