The role of ferroptosis in intervertebral disc degeneration

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.

Circular RNA CircFOXO3 Functions as a Competitive Endogenous RNA for Acid-Sensing Ion Channel Subunit 1 Mediating Oxeiptosis in Nucleus Pulposus

“…Previous studies have shown that exogenous ROS can induce apoptosis, necrosis, autophagy, and ferroptosis in NPCs [ 30 , 31 , 32 ]. To investigate the involvement of these pathways induced in NPCs by TBHP treatment, we utilized various inhibitors, including Z-VAD (a caspase-dependent apoptosis inhibitor), Necrostatin-1 (Nec-1; a necrosis inhibitor), 3-Methyladenine (3-MA; an autophagy inhibitor), Ferrostatin-1 (Fer-1; a ferroptosis inhibitor), and N-Acetyl-L-cysteine (NAC; an ROS inhibitor).…”

Puerarin modulates proliferation, inflammation and ECM metabolism in human nucleus pulposus mesenchymal stem cells via the lncRNA LINC01535

“…Ferroptosis is a unique form of regulated cell death characterized by iron-dependent lipid peroxidation. It has been reported that ferroptosis contributes to the pathogenesis of IVDD [ 47 ]. Puerarin has gained attention for its potential therapeutic effects in various diseases.…”

Ferroptosis-related exosomal non-coding RNAs: promising targets in pathogenesis and treatment of non-malignant diseases

“…A recent focus has been on ferroptosis, triggered by iron and ROS. Ferroptosis is linked to various degenerative disorders, and its role in IDD is emerging ( Fan et al, 2023b ). In the context of IDD, the ncRNA component, particularly circular RNAs present in extracellular vesicles derived from mesenchymal stem cells (MSC-EVs), assumes a critical role in mitigating ferroptosis.…”