2. Academic Validation
  3. The role of autophagy in intervertebral disc degeneration and the regulation mechanism of AP-2α on autophagy

The role of autophagy in intervertebral disc degeneration and the regulation mechanism of AP-2α on autophagy

  • Int J Biochem Cell Biol. 2026 Jan:190:106876. doi: 10.1016/j.biocel.2025.106876.
Jichen He 1,  Wenhao Li 2,  Feng Chen 3,  Guodong Yin 4,  Lin Tang 5,  Qie Fan 6
Affiliations

Affiliations

  • 1 Department of Spine Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, Guangxi 530021, China. Electronic address: [email protected].
  • 2 Department of Spine Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, Guangxi 530021, China. Electronic address: [email protected].
  • 3 Department of Spine Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, Guangxi 530021, China. Electronic address: [email protected].
  • 4 Department of Spine Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, Guangxi 530021, China. Electronic address: [email protected].
  • 5 Department of Spine Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, Guangxi 530021, China. Electronic address: [email protected].
  • 6 Department of Spine Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, Guangxi 530021, China. Electronic address: [email protected].
PMID: 41176025 DOI: 10.1016/j.biocel.2025.106876
Abstract

Autophagy is a promising therapeutic target for intervertebral disc degeneration (IDD). Previous study has shown down-regulation of activator protein 2α (AP-2α) promoted proliferation and inhibited senescence and Apoptosis of rat nucleus pulposus (NP) cells in IDD. This study aimed to investigate the involvement of Autophagy in IDD and the regulatory mechanism of AP-2α on Autophagy. Rat NP cells were exposed to varying concentrations of H2O2. A rat IDD model was constructed and injected with AP-2α low expression adeno-associated virus. To study the role of AP-2α and Autophagy in IDD, we constructed an IDD cell model using H2O2 and treated NP cells with AP-2α low expression adeno-associated virus, Autophagy activator rapamycin (RA) and Autophagy inhibitor 3MA. In vitro, AP-2α (TFAP2A), LC3 (MAP1LC3A/B), Beclin-1 (BECN1), and p62 (Sequestosome 1, SQSTM1) levels were up-regulated after H₂O₂ treatment. In vivo, IDD increased the Apoptosis degree of NP cells, but Apoptosis was reduced after knockdown of AP-2α. Additionally, IDD increased AP-2α, LC3 II/I, Beclin-1, and p62 levels, but knockdown of AP-2α unblocked the Autophagy flow. In vitro, H₂O₂ treatment increased AP-2α, LC3 II/I, Beclin-1, and p62 levels and NP cell Apoptosis. Treatment with RA and its combined knockdown of AP-2α alleviated the dysfunction of Autophagy flow and reduced the degree of Apoptosis. Treatment with 3MA aggravated the dysfunction of Autophagy flow and Apoptosis, which can be alleviated by knockdown of AP-2α. Together, AP-2α regulated Autophagy to participate in the development of IDD in vivo and rat NP cell model of IDD in vitro.

Keywords

AP-2α; Apoptosis; Autophagy; Intervertebral disc degeneration; Nucleus pulposus cells.

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