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

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

doi:10.3389/fcell.2021.787278

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

Front Cell Dev Biol. 2022 Jan 14:9:787278. doi: 10.3389/fcell.2021.787278. eCollection 2021.

Authors

Chenglong Xie^{1

2

3}, Yifeng Shi^{1

2

3}, Zuoxi Chen⁴, Xin Zhou^{1

2}, Peng Luo^{1

2

3}, Chenxuan Hong^{1

2

3}, Naifeng Tian^{1

2

3}, Yaosen Wu^{1

2

3}, Yifei Zhou^{1

2

3}, Yan Lin^{1

2

3}, Haicheng Dou^{1

2

3}, Aimin Wu^{1

2

3}, Qishan Huang^{1

2

3}, Xiaolei Zhang^{1

2

3

5}, Xiangyang Wang^{1

2

3}

Affiliations

¹ Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
² Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China.
³ The Second School of Medicine, Wenzhou Medical University, Wenzhou, China.
⁴ Department of Orthopaedics, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, China.
⁵ Chinese Orthopaedic Regenerative Medicine Society, Hangzhou, China.

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.

Keywords: TFEB; apoptosis; autophagic flux; autophagy; intervertebral disc degeneration; senescence.