Abstract

The purpose of this study was to identify a specific circular RNA and to investigate its regulatory mechanism in intervertebral disc degeneration (IDD). CircGLCE was selected after microarray analyses and was further analysed by RT-qPCR and FISH. CircGLCE was found to stably exist in the cytoplasm of nucleus pulposus (NP) cells. It was downregulated in IDD. After silencing CircGLCE, its function was assessed with RT-qPCR, immunofluorescence analysis and flow cytometry. Knockdown of CircGLCE promoted apoptosis and induced the expression of matrix-degrading enzymes in NP cells. CircGLCE served as a miR-587 sponge in NP cells. Inhibiting miR-587 counteracted the IDD-enhancing effect caused by silencing CircGLCE. STAP1 served as the miRNA target that mediated the functions of miR-587. In an IDD mouse model, the in vivo effects of overexpressing CircGLCE on IDD were confirmed by imaging techniques, TUNEL staining, FISH, western blotting, H&E staining and immunohistochemistry. Thus, CircGLCE attenuates IDD by inhibiting the apoptosis of NP cells and ECM degradation through the targeting of miR-587/STAP1. CircGLCE may be a potential therapeutic target for IDD treatments.

Highlights

  • As the leading illness threatening public health and well-being,[1] various degrees of lower back pain is known to occur in approximately 80% of the global population, and it is the direct cause of chronic disability among 10% of sufferers.[2]

  • CircGLCE served as a miR-587 sponge in nucleus pulposus (NP) cells

  • Inhibiting miR-587 counteracted the Intervertebral disc degeneration (IDD)-enhancing effect caused by silencing CircGLCE

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Summary

Introduction

As the leading illness threatening public health and well-being,[1] various degrees of lower back pain is known to occur in approximately 80% of the global population, and it is the direct cause of chronic disability among 10% of sufferers.[2]. Intervertebral disc degeneration (IDD) can induce profound global socioeconomic burdens. Recent studies have suggested that circular RNAs might have crucial functions in the progression of IDD.

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