Apigenin Alleviates Intervertebral Disc Degeneration via Restoring Autophagy Flux in Nucleus Pulposus Cells.

Chenglong Xie,Xin Zhou,Yan Lin,Chenxuan Hong,Naifeng Tian,Zuoxi Chen,Peng Luo,Haicheng Dou,Yifeng Shi,Qishan Huang,Yifei Zhou,Yaosen Wu,Xiangyang Wang,Xiaolei Zhang,Aimin Wu

doi:10.3389/fcell.2021.787278

Abstract

Oxidative stress–induced apoptosis and senescence of nucleus pulposus (NP) cells play a crucial role in the progression of intervertebral disc degeneration (IVDD). Accumulation of studies has shown that activated autophagy and enhanced autophagic flux can alleviate IVDD. In this study, we explored the effects of apigenin on IVDD in vitro and in vivo. Apigenin was found to inhibit tert-butyl hydroperoxide (TBHP)–induced apoptosis, senescence, and ECM degradation in NP cells. In addition, apigenin treatment can restore the autophagic flux blockage caused by TBHP. Mechanistically, we found that TBHP may induce autophagosome and lysosome fusion interruption and lysosomal dysfunction, while apigenin alleviates these phenomena by promoting the nuclear translocation of TFEB via the AMPK/mTOR signaling pathway. Furthermore, apigenin also exerts a protective effect against the progression of IVDD in the puncture-induced rat model. Taken together, these findings indicate that apigenin protects NP cells against TBHP-induced apoptosis, senescence, and ECM degradation via restoration of autophagic flux in vitro, and it also ameliorates IVDD progression in rats in vivo, demonstrating its potential for serving as an effective therapeutic agent for IVDD.

Highlights

Intervertebral disc degeneration (IVDD) is a worldwide age-related musculoskeletal disease, resulting in low quality of life and an increase in the clinical and socioeconomic burdens (Vergroesen et al, 2015)
Toxicity analysis of apigenin was performed in this study, as observed in Figure 1B, and no cytotoxic effect was found when nucleus pulposus (NP) cells were incubated in various concentrations of apigenin for 24 h; and tert-butyl hydroperoxide (TBHP) decreased the cell viability of NP cells in a dosedependent manner, which was reversed by apigenin treatment (Figures 1C,D)
These results demonstrate that apigenin exerts a protective effect against TBHP-induced apoptosis and senescence in NP cells

Summary

Introduction

Intervertebral disc degeneration (IVDD) is a worldwide age-related musculoskeletal disease, resulting in low quality of life and an increase in the clinical and socioeconomic burdens (Vergroesen et al, 2015). It has been reported that over 40% of low back pain is due to the IVDD progress (Clark and Horton, 2018), which is a consequence of multiple pathological factors, such as abnormal stress, aging, genetic predisposition, and obesity (Kanayama et al, 2009; Ikegawa, 2013). Previous studies indicated that the production of reactive oxygen species (ROS) induced by oxidative stress may increase the level of apoptosis and senescence in NP cells, which may directly affect the ECM anabolism and catabolism (Olga et al, 2016; Feng et al, 2017; Yu et al, 2018). Targeting oxidative stress–induced apoptosis and senescence in NP cells is regarded as an effective therapeutic strategy for alleviating IVDD progress

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Conclusion