Abstract
The molecular mechanism of intervertebral disc degeneration (IVDD) remains unclear. This study aimed to investigate the role of circular RNAs (circRNAs) in the pathogenesis of IVDD. We sued nucleus pulposus (NP) tissues of patients, tert-butyl hydroperoxide (TBHP) stimulated NP cells (NPCs), and IVDD rat model to explore the interaction between circERCC2 and miR-182-5p/SIRT1 axis. The results showed that downregulation of circERCC2 increased the level of miR-182-5p and decreased the level of SIRT1 in degenerative NP tissues in vivo as well as in TBHP-stimulated NPCs in vitro. Treatment of SIRT1-si activated apoptosis and inhibited mitophagy. Moreover, miR-182-5p-si could regulate the mitophagy and the apoptosis of NPCs by targeting SIRT1. The effects of circERCC2 on NPCs and IVDD rat model were mediated by miR-182-5p/SIRT1 axis. In conclusion, this study provides the first evidence that circERCC2 could ameliorate IVDD through miR-182-5p/SIRT1 axis by activating mitophagy and inhibiting apoptosis, and suggests that circERCC2 is a potentially effective therapeutic target for IVDD.
Highlights
Low back pain (LBP) causes high medical costs and socioeconomic burden
CircERCC2 was downregulated in intervertebral disc degeneration (IVDD) and regulated mitophagy and apoptosis
CircERCC2 was downregulated in IVDD based on RNA fluorescence in situ hybridization (FISH) (Fig. 1f)
Summary
Low back pain (LBP) causes high medical costs and socioeconomic burden. The pathogenesis of LBP is poorly understood, intervertebral disc degeneration (IVDD) has been proposed to be the major cause of LBP2,3. IVDD is characterized by increased oxidative stress, the degradation of extracellular matrix (ECM) and apoptosis, and decreased autophagy or mitophagy[4,5]. The main cells in the NP tissues are NP cells (NPCs), which play important roles in ECM degradation[7,8]. In IVDD, NPCs are dysfunctional during the progression of IVDD, causing excessive production of proinflammatory molecules[9,10,11,12,13,14]. The abnormal activities of NPCs could accelerate IVDD. It is important to inhibit the abnormal activities of NPCs to ameliorate IVDD4,15,16
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