Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 236, Issue 4, Pages 2725-2739Publisher
WILEY
DOI: 10.1002/jcp.30039
Keywords
Ferroptosis; intervertebral disc degeneration; NCOA4; oxidative stress
Categories
Funding
- National Natural Science Foundation of China [81672206]
Ask authors/readers for more resources
The study demonstrates the involvement of ferroptosis in the pathogenesis of intervertebral disc degeneration (IVDD) by detecting changes in protein levels and lipid peroxidation during oxidative stress. Treatment with ferroptosis inhibitors and ferritinophagy supports the role of ferroptosis in IVDD.
Ferroptosis is a necrotic form of regulated cell death that was associated with lipid peroxidation and free iron-mediated Fenton reactions. It has been reported that iron deficiency had been implicated in the pathogenesis of intervertebral disc degeneration (IVDD) by activating apoptosis. However, the role of ferroptosis in the process of IVDD has not been illuminated. Here, we demonstrate the involvement of ferroptosis in IVDD pathogenesis. Our in vitro models show the changes in protein levels of ferroptosis marker and enhanced lipid peroxidation level during oxidative stress. Safranin O staining, hematoxylin-eosin staining, and immunohistochemical were used to assess the IVDD after 8 weeks of surgical procedure in vivo. Treatment with ferrostatin-1, deferoxamine, and RSL3 demonstrate the role of ferroptosis intert-butyl hydroperoxide (TBHP)-treated annulus fibrosus cells (AFCs) and nucleus pulposus cells (NPCs). Ferritinophagy, nuclear receptor coactivator 4 (NCOA4)-mediated ferritin selective autophagy, is originated during the process of ferroptosis in response to TBHP treatment. Knockdown and overexpression NCOA4 further prove TBHP may induce ferroptosis of AFCs and NPCs in an autophagy-dependent way. These findings support a role for oxidative stress-induced ferroptosis in the pathogenesis of IVDD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available