2. Academic Validation
  3. Knocking down EGR1 inhibits nucleus pulposus cell senescence and mitochondrial damage through activation of PINK1-Parkin dependent mitophagy, thereby delaying intervertebral disc degeneration

Knocking down EGR1 inhibits nucleus pulposus cell senescence and mitochondrial damage through activation of PINK1-Parkin dependent mitophagy, thereby delaying intervertebral disc degeneration

  • Free Radic Biol Med. 2024 Aug 14:224:9-22. doi: 10.1016/j.freeradbiomed.2024.08.015.
Zuo-Long Wu 1,  Ke-Ping Wang 2,  Ya-Jun Chen 3,  Wei Song 1,  Yong Liu 1,  Kai-Sheng Zhou 1,  Peng Mao 1,  Zhong Ma 1,  Hai-Hong Zhang 4
Affiliations

Affiliations

  • 1 Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China; The Second Clinical Medical College, Lanzhou University, Lanzhou, China; Key Laboratory of Orthopedics Disease of Gansu Province, Lanzhou University Second Hospital, Lanzhou, China.
  • 2 Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China; The Second Clinical Medical College, Lanzhou University, Lanzhou, China; Key Laboratory of Orthopedics Disease of Gansu Province, Lanzhou University Second Hospital, Lanzhou, China. Electronic address: wangkeping2004@163.com.
  • 3 Lanzhou Maternal and Child Health Hospital, Lanzhou, China.
  • 4 Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China; The Second Clinical Medical College, Lanzhou University, Lanzhou, China; Key Laboratory of Orthopedics Disease of Gansu Province, Lanzhou University Second Hospital, Lanzhou, China. Electronic address: zhanghaihong1949@163.com.
PMID: 39151834 DOI: 10.1016/j.freeradbiomed.2024.08.015
Abstract

Mitophagy plays a crucial role in maintaining the homeostasis of intervertebral disc (IVD). Early Growth Response 1 (EGR1), a conservative transcription factor, is commonly upregulated under oxidative stress conditions and participates in regulating cellular senescence, Apoptosis, and inflammatory responses. However, the specific role of EGR1 in nucleus pulposus (NP) cell senescence and Mitophagy remains unclear. In this study, through bioinformatics analysis and validation using human tissue specimens, we found that EGR1 is significantly upregulated in IVD degeneration (IDD). Further experimental results demonstrate that knockdown of EGR1 inhibits TBHP-induced NP cell senescence and mitochondrial dysfunction while promoting the activation of Mitophagy. The protective effect of EGR1 knockdown on NP cell senescence and mitochondrion disappears upon inhibition of Mitophagy with mdivi1. Mechanistic studies reveal that EGR1 suppresses NP cell senescence and mitochondrial dysfunction by modulating the PINK1-Parkin dependent Mitophagy pathway. Additionally, EGR1 knockdown delays acupuncture-induced IDD in rats. In conclusion, our study demonstrates that under TBHP-induced oxidative stress, EGR1 knockdown mitigates NP cell senescence and mitochondrial dysfunction through the PINK1-Parkin dependent Mitophagy pathway, thereby alleviating IDD.

Keywords

Cell senescence; EGR1; IDD; Mitophagy; Oxidative stress; PINK1; Parkin.

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