No Genetic Causal Association between Iron Status and Intervertebral Disc Degeneration: A Two-Sample Mendelian Randomization Study DOI Creative Commons

Hewen Li,

Chen’guang Su,

Rongbo Yu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 14, 2024

Abstract Many clinical and basic studies have shown an association between iron status intervertebral disc degeneration (IVDD). However, their causal relationship is still unclear. The aim of this study was to explore the genetic causality IVDD using Mendelian randomization. Random effects inverse variance weighted (IVW) meta-analysis primary method analysis, with MR‒Egger, median, simple modal, modal methods as secondary methods. Subsequently, we used IVW, MR-PRESSO, leave-one-out analyses test for heterogeneity horizontal pleiotropy. Finally, maximum likelihood, penalized median IVW (fixed effects) further verify reliability results. Random-effects meta-analyses revealed that transferrin, total binding capacity (TIBC), ferritin, iron, transferrin saturation (TSAT) were not genetically causally related IVDD, removal outliers detected by MR-PRESSO resulted in broad consistency. Our there no but it cannot be excluded a correlation two at level other than genetics.

Language: Английский

Polydopamine Nanoparticles Targeting Ferroptosis Mitigate Intervertebral Disc Degeneration Via Reactive Oxygen Species Depletion, Iron Ions Chelation, and GPX4 Ubiquitination Suppression DOI Creative Commons
Xiao Yang, Yan Chen,

Jiadong Guo

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(13)

Published: March 23, 2023

Intervertebral disc degeneration (IVDD)-induced lower back pain (LBP) is a common problem worldwide. The underlying mechanism partially accredited to ferroptosis, based on sequencing analyses of IVDD patients from the gene expression omnibus (GEO) databases. In this study, it shown that polydopamine nanoparticles (PDA NPs) inhibit oxidative stress-induced ferroptosis in nucleus pulposus (NP) cells vitro. PDA NPs scavenge reactive oxygen species (ROS), chelate Fe

Language: Английский

Citations

91
The mechanisms and functions of IL-1β in intervertebral disc degeneration DOI Creative Commons
Hongtao Li, Xiaoqiang Wang, Hongyu Pan

et al.

Experimental Gerontology, Journal Year: 2023, Volume and Issue: 177, P. 112181 - 112181

Published: April 24, 2023

Intervertebral disc degeneration (IDD) is the leading cause of low back pain (LBP) and disability in elderly, imposing significant public health economic burden worldwide. Meanwhile, pathological mechanisms IDD remain complicated, treatment strategy to reverse primarily due unclear specific lack particular effective targets. Interleukin-1β (IL-1β), one most important members IL-1 family, can induce solid pro-inflammatory activity by stimulating secretion various mediators considered key mediator. However, recent years, IL-1β be able regulate IVD cell death many ways, such as apoptosis, pyroptosis, ferroptosis, so on. At same time, numerous studies on inhibitors suggest that inhibition may a promising biological therapy for IDD. Many have been investigated through pathogenic mechanisms, including inhibiting inflammatory processes, regulating ECM degradation, more. Therefore, anti-IL-1β effect alleviating degeneration. This article mainly reviews functions investigates advances biotherapeutic approach

Language: Английский

Citations

33
The role of ferroptosis in intervertebral disc degeneration DOI Creative Commons

Chun‐Yang Fan,

Genglei Chu, Zilin Yu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: July 27, 2023

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

Language: Английский

Citations

31
Exploration of the mode of death and potential death mechanisms of nucleus pulposus cells DOI

Daqian Zhou,

Yongliang Mei,

Chao Song

et al.

European Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 54(9)

Published: April 17, 2024

Intervertebral disc degeneration (IVDD) is a common chronic orthopaedic disease in orthopaedics that imposes heavy economic burden on people and society. Although it well established IVDD associated with genetic susceptibility, ageing obesity, its pathogenesis remains incompletely understood. Previously, was thought to occur because of excessive mechanical loading leading destruction nucleus pulposus cells (NPCs), but studies have shown much more complex process inflammation, metabolic factors NPCs death can involve all parts the disc, characterized by causing extracellular matrix (ECM) degradation. The damage pattern like some programmed cell death, suggesting death. apoptosis pyroptosis been studied IVDD, intervertebral still not be fully elucidated using only traditional modalities. With increasing research, new modes PANoptosis, ferroptosis senescence found closely related degeneration. Among these, PANoptosis combines essential elements pyroptosis, necroptosis form highly coordinated dynamically balanced inflammatory process. Furthermore, we believe may also crosstalk senescence. Therefore, review progress research multiple deaths provide guidance for clinical treatment.

Language: Английский

Citations

12
ROS‐Responsive Injectable Hydrogel Loaded with SLC7A11‐modRNA Inhibits Ferroptosis and Mitigates Intervertebral Disc Degeneration in Rats DOI

Tian Gao,

Guangyu Xu, Tiancong Ma

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(27)

Published: May 1, 2024

Abstract Intervertebral disc degeneration (IVDD) is the primary cause of low back pain, with oxidative stress being a recognized factor that causes its development. Presently, pain imposes significant global economic burden. However, effectiveness treatments for IVDD remains extremely limited. Therefore, this study aims to explore innovative and effective by focusing on as starting point. In study, an injectable reactive oxygen species‐responsive hydrogel (PVA‐tsPBA@SLC7A11 modRNA) developed, designed achieve rapid loading selective release chemically synthesized modified mRNA (modRNA). SLC7A11 modRNA specifically used upregulate expression ferroptosis marker SLC7A11. The local injection PVA‐tsPBA@SLC7A11 into degenerated intervertebral (IVD) results in cleavage PVA‐tsPBA, leading enclosed modRNA. extent directly proportional severity IVDD, ultimately ameliorating inhibiting nucleus pulposus cells (NPCs). This proposes system PVA‐tsPBA hydrogel‐encapsulated modRNA, representing potential novel treatment strategy patients early‐stage IVDD.

Language: Английский

Citations

10
Neurotoxicity of manganese via ferroptosis induced by redox imbalance and iron overload DOI Creative Commons

Changyong Wang,

Hongyan Zhao, Yaoyang Liu

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 278, P. 116404 - 116404

Published: May 4, 2024

Manganese (Mn) is an essential trace element for maintaining bodily functions. Excessive exposure to Mn can pose serious health risks humans and animals, particularly the nervous system. While has been implicated as a neurotoxin, exact mechanism of its toxicity remains unclear. Ferroptosis form programmed cell death that results from iron-dependent lipid peroxidation. It plays role in various physiological pathological cellular processes may be closely related Mn-induced neurotoxicity. However, ferroptosis neurotoxicity not thoroughly investigated. Therefore, this study aims investigate Using bioinformatics, we identified significant changes genes associated with Mn-exposed animal models. We then evaluated at both levels. Our findings suggest causes weight loss system damage mice. In vitro vivo experiments have shown increases malondialdehyde, reactive oxygen species, ferrous iron, while decreasing glutathione adenosine triphosphate. These leads increase peroxidation disrupts iron metabolism, resulting oxidative stress injury ferroptosis. Furthermore, assessed expression levels proteins mRNAs ferroptosis, confirming involvement

Language: Английский

Citations

10
Inhibiting DNA methyltransferase DNMT3B confers protection against ferroptosis in nucleus pulposus and ameliorates intervertebral disc degeneration via upregulating SLC40A1 DOI Creative Commons
Jiaxing Chen, Xinyu Yang, Qiaochu Li

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 220, P. 139 - 153

Published: May 3, 2024

Epigenetic changes are important considerations for degenerative diseases. DNA methylation regulates crucial genes by epigenetic mechanism, impacting cell function and fate. presents hypermethylation in degenerated nucleus pulposus (NP) tissue, but its role intervertebral disc degeneration (IVDD) remains elusive. This study aimed to demonstrate that methyltransferase mediated was responsible IVDD integrative bioinformatics experimental verification. Methyltransferase DNMT3B highly expressed severely NP tissue (involving human rats) in-vitro cells (NPCs). Bioinformatics elucidated hypermethylated were enriched oxidative stress ferroptosis, the ferroptosis suppressor gene SLC40A1 identified with lower expression higher tissue. Cell culture using NPCs showed induced downregulating SLC40A1, promoting a phenotype. An in-vivo rat model inhibitor 5-AZA alleviated puncture-induced IVDD. Taken together, aggravates via regulating SLC40A1. mechanism within is promising therapeutic biomarker

Language: Английский

Citations

7
Humanin reduces nucleus pulposus cells ferroptosis to alleviate intervertebral disc degeneration: An in vitro and in vivo study DOI Creative Commons
Daxue Zhu,

Zhaoheng Wang,

Yanhu Li

et al.

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 50, P. 274 - 294

Published: Jan. 1, 2025

Language: Английский

Citations

1
Magnetically attracting hydrogel reshapes iron metabolism for tissue repair DOI Creative Commons
Yichang Xu, Feng Cai,

Yidi Zhou

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(33)

Published: Aug. 16, 2024

Ferroptosis, caused by disorders of iron metabolism, plays a critical role in various diseases, making the regulation metabolism essential for tissue repair. In our analysis degenerated intervertebral disc tissue, we observe positive correlation between concentration extracellular ions (ex-iron) and severity ferroptosis degeneration (IVDD). Hence, inspired magnets attracting metals, combine polyether F127 diacrylate (FDA) with tannin (TA) to construct magnetically hydrogel (FDA-TA). This demonstrates capability adsorb ex-iron remodel cells. Furthermore, it exhibits good toughness self-healing properties. Notably, can activate PI3K-AKT pathway inhibit nuclear receptor coactivator 4–mediated ferritinophagy under enrichment conditions. The curative effect related mechanism are further confirmed vivo. Consequently, on basis pathological mechanism, targeted is designed reshape offering insights

Language: Английский

Citations

4
Ferroptosis: A Frontier in Osteoporosis DOI

Shubhrat Maheshwari,

Aditya Singh, Amita Verma

et al.

Hormone and Metabolic Research, Journal Year: 2024, Volume and Issue: 56(09), P. 625 - 632

Published: Feb. 2, 2024

Reduced bone mass and degeneration of the microarchitecture tissue are hallmarks osteoporosis, a metabolic disease that increases skeletal fragility fracture susceptibility. Osteoporosis is primarily caused by unbalanced remodeling, in which synthesis outpaced resorption osteoclasts. Along with bone-building vitamins calcium vitamin D, typical medications for treating osteoporosis include bisphosphonates calcitonin. The present therapies effectively stop osteoclast activation too high, however they come varying degrees negative effects. Numerous factors can contribute to characterized loss density due deterioration bone's microstructure, makes more fragile. As result, it systemic condition patients likely fracture. Interest function ferroptosis pathophysiology developing. In this review, we go through shape cell, fundamental mechanisms ferroptosis, relationship between osteoclasts osteoblasts, association diabetic steroid-induced postmenopausal osteoporosis. functions cellular function, signaling cascades, pharmacological inhibition, gene silencing have been better understood thanks recent advances biomedical research.

Language: Английский

Citations

3