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Review
. 2023 Jul 27:11:1219840.
doi: 10.3389/fcell.2023.1219840. eCollection 2023.

The role of ferroptosis in intervertebral disc degeneration

Chunyang Fan  1 , Genglei Chu  1 , Zilin Yu  1 , Zhongwei Ji  1   2 , Fanchen Kong  1 , Lingye Yao  1 , Jiale Wang  1 , Dechun Geng  1 , Xiexing Wu  1 , Haiqing Mao  1
Affiliations
Review

The role of ferroptosis in intervertebral disc degeneration

Chunyang Fan et al. Front Cell Dev Biol. .

Abstract

Nucleus pulposus, annulus fibrosus, and cartilage endplate constitute an avascular intervertebral disc (IVD), which is crucial for spinal and intervertebral joint mobility. As one of the most widespread health issues worldwide, intervertebral disc degeneration (IVDD) is recognized as a key contributor to back and neck discomfort. A number of degenerative disorders have a strong correlation with ferroptosis, a recently identified novel regulated cell death (RCD) characterized by an iron-dependent mechanism and a buildup of lipid reactive oxygen species (ROS). There is growing interest in the part ferroptosis plays in IVDD pathophysiology. Inhibiting ferroptosis has been shown to control IVDD development. Several studies have demonstrated that in TBHP-induced oxidative stress models, changes in ferroptosis marker protein levels and increased lipid peroxidation lead to the degeneration of intervertebral disc cells, which subsequently aggravates IVDD. Similarly, IVDD is significantly relieved with the use of ferroptosis inhibitors. The purpose of this review was threefold: 1) to discuss the occurrence of ferroptosis in IVDD; 2) to understand the mechanism of ferroptosis and its role in IVDD pathophysiology; and 3) to investigate the feasibility and prospect of ferroptosis in IVDD treatment.

Keywords: antioxidant system; epigenetics; ferroptosis; intervertebral disc degeneration; lipid peroxidation; reactive oxygen species.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Pathological changes in healthy and degenerative IVD. Degenerative IVD will produce metabolic disorders, extracellular matrix degeneration, inflammation, and a series of programmed cell death (including necrosis, apoptosis, pyroptosis, ferroptosis, etc.).
FIGURE 2
FIGURE 2
The developmental history of ferroptosis and ferroptosis in IVDD.
FIGURE 3
FIGURE 3
The latest reported mechanism of ferroptosis. The essential feature of ferroptosis is the imbalance between oxidative stress and anti-oxidative stress system. This article reviews the pathogenesis of ferroptosis, including its occurrence mechanism, regulation mechanism and typical inhibitors (Table 2).
FIGURE 4
FIGURE 4
Modulating ferroptosis in IVDD by small molecule compounds and epigenetic modifications.
See this image and copyright information in PMC

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