2. Academic Validation
  3. The sonic hedgehog pathway suppresses oxidative stress and senescence in nucleus pulposus cells to alleviate intervertebral disc degeneration via GPX4

The sonic hedgehog pathway suppresses oxidative stress and senescence in nucleus pulposus cells to alleviate intervertebral disc degeneration via GPX4

  • Biochim Biophys Acta Mol Basis Dis. 2023 Nov 16;1870(2):166961. doi: 10.1016/j.bbadis.2023.166961.
Yong Zhuang 1,  Libangxi Liu 2,  Miao Liu 1,  Jiawei Fu 2,  Xuezheng Ai 2,  Dan Long 2,  Xue Leng 2,  Yang Zhang 2,  Xunren Gong 3,  Xianwen Shang 1,  Changqing Li 2,  Bo Huang 2,  Yue Zhou 2,  Xu Ning 4,  Shiwu Dong 5,  Chencheng Feng 6
Affiliations

Affiliations

  • 1 Department of Orthopedics, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, PR China.
  • 2 Department of Orthopedics, Xinqiao Hospital, Army Medical University, Chongqing 400037, PR China.
  • 3 Xinqiao Hospital, Army Medical University, Chongqing 400037, PR China.
  • 4 Department of Orthopedics, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, PR China. Electronic address: [email protected].
  • 5 Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, PR China; State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing 400038, PR China. Electronic address: [email protected].
  • 6 Department of Orthopedics, Xinqiao Hospital, Army Medical University, Chongqing 400037, PR China. Electronic address: [email protected].
PMID: 37979732 DOI: 10.1016/j.bbadis.2023.166961
Abstract

Disruption of intervertebral disc (IVD) homeostasis caused by oxidative stress and nucleus pulposus cell (NPC) senescence is a main cause of intervertebral disc degeneration (IDD). The sonic Hedgehog (Shh) pathway plays an important role in IVD development, but its roles in IDD are unknown. This study aimed to investigate the effects of the Shh pathway on the alleviation of IDD and the related mechanisms. In vivo, the effect of the Shh pathway on IVD homeostasis was studied by intraperitoneal injection of recombinant Shh (rShh) and GANT61 based on puncture-induced IDD. GANT61, lentivirus-coated sh-Gli1 and rShh were used to investigate the role and mechanism of the Shh pathway in NPCs based on senescence induced by Braco19 and oxidative stress induced by TBHP. Shh pathway expression decreased, and senescence and oxidative stress increased with age. Intraperitoneal injection of rShh activated the Shh pathway to suppress oxidative stress and NPC senescence and consequently alleviated needle puncture-induced IDD. In vitro, the Shh pathway upregulated Glutathione Peroxidase 4 (GPX4) expression to suppress oxidative stress and senescence in NPCs. Moreover, GPX4 suppression in NPCs by si-GPX4 significantly reduced the protective effect of the Shh pathway on oxidative stress and senescence in NPCs. Our results demonstrate for the first time that the Shh pathway plays a key role in the alleviation of IDD by suppressing oxidative stress and cell senescence in NP tissues. This study provides a new potential target for the prevention and reversal of IDD.

Keywords

Cell senescence; Glutathione peroxidase 4; Intervertebral disc degeneration; Oxidative stress; Sonic hedgehog pathway.

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