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

Frontiers in Cell and Developmental Biology

Xiaolei Zhang¹  Zuoxi Chen³  Xin Zhou⁴  Chenglong Xie⁵  Haicheng Dou⁵  Aimin Wu⁵  Yaosen Wu⁵  Yifeng Shi⁵  Naifeng Tian⁵  Peng Luo⁵  Qishan Huang⁵  Chenxuan Hong⁵  Yifei Zhou⁵  Yan Lin⁵  Xiangyang Wang⁵ 

[1] Chinese Orthopaedic Regenerative Medicine Society, Hangzhou, China;Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China;Department of Orthopaedics, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, China;Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China;The Second School of Medicine, Wenzhou Medical University, Wenzhou, China;

关键词: intervertebral disc degeneration;    autophagy;    autophagic flux;    apoptosis;    senescence;    TFEB;   

DOI  :  10.3389/fcell.2021.787278

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown