Involvement of oxidative stress‐induced annulus fibrosus cell and nucleus pulposus cell ferroptosis in intervertebral disc degeneration pathogenesis

Yang, Runze; Xu, Wen-Ning; Zheng, Huo‐Liang; Zheng, Xianxu; Li, Bo; Jiang, Lei‐Sheng; Jiang, Sheng‐Dan

doi:10.1002/jcp.30039

Cited by 122 publications

(126 citation statements)

References 44 publications

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“…Ferroptosis is involved in pathological cell death associated with ischemia-reperfusion injury, stroke, carcinogenesis, kidney injury, and degenerative diseases such as Parkinson's, Huntington's, and Alzheimer's diseases [ 14 ]. Additionally, some studies found that ferroptosis may also play an important role in IVDD [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Ferroportin‐Dependent Iron Homeostasis Protects against Oxidative Stress‐Induced Nucleus Pulposus Cell Ferroptosis and Ameliorates Intervertebral Disc Degeneration In Vivo

Song

Luo

et al. 2021

Oxidative Medicine and Cellular Longevity

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Ferroptosis is a specialized form of regulated cell death that is charactered by iron-dependent lethal lipid peroxidation, a process associated with multiple diseases. However, its role in the pathogenesis of intervertebral disc degeneration (IVDD) is rarely investigated. This study is aimed at investigating the role of ferroptosis in oxidative stress- (OS-) induced nucleus pulposus cell (NPC) decline and the pathogenesis of IVDD and determine the underlying regulatory mechanisms. We used tert-butyl hydroperoxide (TBHP) to simulate OS conditions around human NPCs. Flow cytometry and transmission electron microscopy were used to identify ferroptosis, while iron assay kit, Perl’s staining, and western blotting were performed to assay the intracellular iron levels. A ferroportin- (FPN-) lentivirus and FPN-siRNA were constructed and used to explore the relationship between FPN, intracellular iron homeostasis, and ferroptosis. Furthermore, hinokitiol, a bioactive compound known to specifically resist OS and restore FPN function, was evaluated for its therapeutic role in IVDD both in vitro and in vivo. The results indicated that intercellular iron overload plays an essential role in TBHP-induced ferroptosis of human NPCs. Mechanistically, FPN dysregulation is responsible for intercellular iron overload under OS. The increase in nuclear translocation of metal-regulatory transcription factor 1 (MTF1) restored the function of FPN, abolished the intercellular iron overload, and protected cells against ferroptosis. Additionally, hinokitiol enhanced the nuclear translocation of MTF1 by suppressing the JNK pathway and ameliorated the progression of IVDD in vivo. Taken together, our results demonstrate that ferroptosis and FPN dysfunction are involved in the NPC depletion and the pathogenesis of IVDD under OS. To the best of our knowledge, this is the first study to demonstrate the protective role of FPN in ferroptosis of NPCs, suggesting its potential used as a novel therapeutic target against IVDD.

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Section: Introductionmentioning

confidence: 99%

Ferroportin‐Dependent Iron Homeostasis Protects against Oxidative Stress‐Induced Nucleus Pulposus Cell Ferroptosis and Ameliorates Intervertebral Disc Degeneration In Vivo

Song

Luo

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Therefore, the rigor of the definition of ferroptosis is still worth discussing because of its great significance for related pathological diseases. As ferroptosis overlaps with autophagy, apoptosis, and oxidative stress [23][24][25][26], using biochemical ferroptosis biomarkers only to judge the occurrence or participation of ferroptosis is controversial because such a classification cannot exclude the pseudoferroptotic performance caused by other pathological factors.…”

Section: The Characteristics Of Ferroptosismentioning

confidence: 99%

The Cross‐Link between Ferroptosis and Kidney Diseases

Wang

Liu

Wang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Acute and chronic kidney injuries result from structural dysfunction and metabolic disorders of the kidney in various etiologies, which significantly affect human survival and social wealth. Nephropathies are often accompanied by various forms of cell death and complex microenvironments. In recent decades, the study of kidney diseases and the traditional forms of cell death have improved. Nontraditional forms of cell death, represented by ferroptosis and necroptosis, have been discovered in the field of kidney diseases, which have reshuffled the role of traditional cell death in nephropathies. Although interactions between ferroptosis and acute kidney injury (AKI) have been continuously explored, studies on ferroptosis and chronic kidney disease (CKD) remain limited. Here, we have reviewed the therapeutic significance of ferroptosis in AKI and anticipated the curative potential of ferroptosis for CKD in the hope of providing insights into ferroptosis and CKD.

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“…Only two studies described senescence ( 24 , 25 ), and one study discussed mitophagy in IDD ( 25 ). Therefore, the important phenotypes mediated by circRNAs, including cellular senescence, autophagy, mitophagy and ferroptosis, in IDD have not been sufficiently illuminated ( 50 , 57 , 66 , 67 ).…”

Section: Limitations and Future Directionsmentioning

confidence: 99%

Roles of circular RNAs in the pathogenesis of intervertebral disc degeneration (Review)

Lin

et al. 2021

Exp Ther Med

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Lower back pain (LBP) is an extremely common symptom and is recognized as a leading contributor to disability and disease burden globally. Intervertebral disc degeneration (IDD) represents a major cause of LBP. However, the molecular mechanisms involved in the pathogenesis of IDD remain unclear, and currently available treatments, including conservative and surgical options, fail to effectively delay, stop or reverse the progression of IDD. Circular RNAs (circRNAs) are a newly discovered group of covalently closed, single-stranded and endogenous non-coding RNAs. A growing body of research has revealed that a number of circRNAs are widely and aberrantly expressed in IDD tissues. Furthermore, they play important roles in the pathogenesis of IDD, including proliferation, apoptosis, senescence, mitophagy, inflammation and extracellular matrix metabolism, mainly by acting as sponges for microRNAs. The present review aims to summarize the current understanding on the mechanisms of circRNA-mediated regulation in IDD.

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Involvement of oxidative stress‐induced annulus fibrosus cell and nucleus pulposus cell ferroptosis in intervertebral disc degeneration pathogenesis

Cited by 122 publications

References 44 publications

Ferroportin‐Dependent Iron Homeostasis Protects against Oxidative Stress‐Induced Nucleus Pulposus Cell Ferroptosis and Ameliorates Intervertebral Disc Degeneration In Vivo

Ferroportin‐Dependent Iron Homeostasis Protects against Oxidative Stress‐Induced Nucleus Pulposus Cell Ferroptosis and Ameliorates Intervertebral Disc Degeneration In Vivo

The Cross‐Link between Ferroptosis and Kidney Diseases

Roles of circular RNAs in the pathogenesis of intervertebral disc degeneration (Review)

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