MUC1 and CREB3 are Hub Ferroptosis Suppressors for Nucleus Pulposus and Annulus Fibrosus Degeneration by Integrated Bioinformatics and Experimental Verification DOI Creative Commons
Xinyu Yang, Qiaochu Li, Linbang Wang

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 8965 - 8984

Published: Nov. 1, 2024

Ferroptosis is an underlying mechanism for various degenerative diseases, but its role in intervertebral disc degeneration remains elusive. This study aims to explore the key ferroptosis-related genes and nucleus pulposus (NP) annulus fibrosus (AF) degeneration. We analyzed gene expression profiles of NP AF from Gene Expression Omnibus database. The differentially expressed (FRDEGs) degenerated were filtered, followed by GO KEGG analysis. Feature FRDEGs identified LASSO SVM-RFE algorithms, then Set Enrichment Analysis (GSEA) Variation (GSVA) conducted. Immune infiltration analysis was conducted CIBERSORT algorithm. established drug networks via Drug-Gene Interaction Database competitive endogenous RNA (ceRNA) miRanda, miRDB, TargetScan levels feature assessed validation sets, single-cell RNA-seq, experimental verification. A total 15 18 obtained AF, respectively. revealed their implication oxidative stress. Four (AKR1C1, AKR1C3, MUC1, ENPP2) five (SCP2, ABCC1, KLF2, IDO1, CREB3) GSEA GSVA showed that these enriched lots biological functions, including immune response. CREB3 negatively correlated with Eosinophils drugs ceRNAs targeting MUC1 identified. Experimental verification RNA-seq downregulated considered novel biomarkers ferroptosis, Drug ceRNA constructed future development investigation new mechanisms ferroptosis.

Language: Английский

Electroacupuncture regulates SIRT1/p53/p21 signaling pathway to prevent stress-induced premature senescence of nucleus pulposus cells in degenerative intervertebral discs DOI
Min Wang, Jiabao Huang, Jing Zou

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114114 - 114114

Published: Jan. 31, 2025

Language: Английский

Citations

1
Molecular mechanism of mechanical pressure induced changes in the microenvironment of intervertebral disc degeneration DOI
Fei Liu, Chao Song, Lei Yang

et al.

Inflammation Research, Journal Year: 2024, Volume and Issue: 73(12), P. 2153 - 2164

Published: Oct. 8, 2024

Language: Английский

Citations

5
Therapeutic potential of targeting the IRF2/POSTN/Notch1 axis in nucleus pulposus cells for intervertebral disc degeneration DOI Creative Commons
Daxue Zhu,

Zhaoheng Wang,

Shi‐Jie Chen

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 22, 2025

Intervertebral disc degeneration (IDD) is a leading cause of low back pain, often linked to inflammation and pyroptosis in nucleus pulposus (NP) cells. The role Periostin (POSTN) IDD remains unclear. This study aims investigate the influence POSTN on NLRP3 inflammasome activation NP cells during IDD. IVD samples were collected from patients undergoing spinal surgery classified according Pfirrmann grading system. Human cultured treated with IL-1β induce pyroptotic phenotype. Western blotting, Immunofluorescence (IF), immunohistochemistry (IHC) assessed expression levels relevant proteins. Chromatin immunoprecipitation (ChIP) luciferase reporter assays verified binding IRF2 GSDMD promoters evaluated target genes. severity was using MRI histological analysis. Deletion significantly alleviated by suppressing activity found aggravate cell activating through NF-κB (P65) cGAS/STING signaling pathways. Furthermore, interacted Notch1 expression. identified as regulator at transcriptional level, contributing pyroptosis. also directly induced GSDMD, mediating Chemical screening Glucosyringic acid (GA) direct inhibitor POSTN, which delayed progression. elucidates pivotal highlights GA promising therapeutic candidate for These findings provide new insights into molecular mechanisms potential avenues treatment.

Language: Английский

Citations

0
ASIC1a mediated nucleus pulposus cells pyroptosis and glycolytic crosstalk as a molecular basis for intervertebral disc degeneration DOI
Chao Song, Fei Liu, Xiaofei Wu

et al.

Inflammation Research, Journal Year: 2025, Volume and Issue: 74(1)

Published: Jan. 28, 2025

Language: Английский

Citations

0
Adipose Tissue-Derived Exosome Maintains Metabolic Balance of Extracellular Matrix in Rat Nucleus Pulposus Cells DOI Creative Commons

Ruoyu Zhao,

Lei Ma,

Joan Li

et al.

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 2411 - 2425

Published: Feb. 1, 2025

This study aimed to investigate the protective effect of adipose tissue-derived exosomes (AT-Exo) on rat nucleus pulposus cells (NPCs). Ultracentrifugation was used extract from tissue. Transmission electron microscopy (TEM), Western blot, and nanoparticle tracking analysis (NTA) were characterize exosomes. Tert-butyl hydrogen peroxide (TBHP) induce apoptosis NPCs. Cell viability determined by CCK-8 assay. AT-Exo administered its NPCs using blot immunofluorescence staining. successfully extracted characterized NTA, TEM, blots. Uptake assay showed that can be taken up TBHP (60 μM) resulted in decreased cell increased Interestingly, protected against TBHP, indicated viability, apoptosis, upregulated Aggrecan type II collagen deposition, downregulated matrix metalloproteinase 3/13. In summary, increase levels Aggrecan, collagen, Bcl2, decrease 3/13, cleaved caspase3, Bax. Therefore, maintain metabolic balance extracellular protect cells.

Language: Английский

Citations

0
Low-intensity ultrasound stimulation promotes differentiation of bone marrow mononuclear cells to nucleus pulposus cells for matrix synthesis DOI
Chuang Li, Yuxi He, Ruosi Chen

et al.

American Journal of Translational Research, Journal Year: 2025, Volume and Issue: 17(2), P. 927 - 940

Published: Jan. 1, 2025

To investigate the role of low-intensity ultrasound stimulation (LIUS) in facilitating differentiation bone marrow mononuclear cells (BMMNCs) into nucleus pulposus (NPCs) for matrix synthesis, offering a possible new therapeutic approach intervertebral disc degeneration. Human BMMNCs and NPCs were cultured, exosomes extracted from using differential ultracentrifugation, followed by characterization. LIUS was utilized to evaluate exosome uptake, induce cell differentiation, measure apoptosis, track DNA synthesis EdU assays. Various experimental conditions tested, including different intensities durations. A range detection techniques, such as RT-qPCR, western blotting, cellular staining, employed monitor relevant indicators. Exosomes successfully isolated NPCs, their purity confirmed nanoparticle tracking analysis (NTA), transmission electron microscopy, blot. PKH67-labeled internalized during co-incubation. treatment at revealed that LIUS-100 group exhibited most significant proliferation, shown Flow cytometry LIUS-150 groups demonstrated pronounced inhibition apoptosis. In NPC exosome-induced experiments, expression marker mRNA protein levels increased over time under standard conditions, with even greater upregulation observed stimulation. Moreover, enhanced intracellular accumulation glycosaminoglycans proteoglycans, suggesting its promoting BMMNC component synthesis. are essential guiding representing promising strategy However, further vivo studies needed refine technique, ensure safety, long-term efficacy.

Language: Английский

Citations

0
Oxidized low-density lipoprotein induced ferroptosis in nucleus pulposus cell contributes to intervertebral disc degeneration via LOX-1/NF-κB/NOX signal DOI

Zhonghan Liu,

Xinhua Li, Jie Pan

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 153, P. 114455 - 114455

Published: March 20, 2025

Language: Английский

Citations

0
Novel Anti-pyroptosis Drug Loaded on Metal-organic Framework for Intervertebral Disc Degeneration Therapy DOI Creative Commons

Yekai Zhang,

Jiawei Qiu,

Yiji Chen

et al.

Materials Today Bio, Journal Year: 2025, Volume and Issue: unknown, P. 101729 - 101729

Published: April 1, 2025

Intervertebral disc degeneration (IVDD) is the main cause of low back pain, pyroptosis a major contributor to various diseases, including IVDD; however, there currently no effective drugs targeting for therapy. In this study, we established model in nucleus pulposus cells (NPCs) vitro and searched inhibitors FDA Medicine Library. High throughput screening study revealed that Pirfenidone (PFD) was most inhibitor among 1500+ drugs, which confirmed by further experiments. As administering PFD alone may lead poor efficacy due short action time bioavailability, designed smart delivery system PFD. A pH-responsive metal-organic framework (MOF), poly-His6-zinc (PHZ) assembly, loaded with (PFD@PHZ) IVDD PHZ shown have excellent lysosomal escape properties bioavailability addition, release PDF from PFD@PHZ could be triggered acidic microenvironment degenerated intervertebral discs. also effectively inhibit pyroptosis, senescence, extracellular matrix (ECM) degradation NPCs, both vivo, thereby mitigating progression rats. Thus, current shows as novel potential nanomaterial efficient

Language: Английский

Citations

0
“Dictionary of immune responses” reveals the critical role of monocytes and the core target IRF7 in intervertebral disc degeneration DOI Creative Commons

Peichuan Xu,

Kaihui Li, Jinghong Yuan

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 17, 2024

Intervertebral disc degeneration (IDD) is widely regarded as the primary contributor to low back pain(LBP). As an immune-privileged organ, upon onset of IDD, various components nucleus pulposus (NP) are exposed host's immune system, accumulating cytokines. Cytokines facilitate intercellular communication within induce cells polarisation, and exacerbate oxidative stress in IDD.

Language: Английский

Citations

2
Research progress on long non‑coding RNAs in non‑infectious spinal diseases (Review) DOI

Zhong Ma,

Xin Liu,

Xianxu Zhang

et al.

Molecular Medicine Reports, Journal Year: 2024, Volume and Issue: 30(3)

Published: July 9, 2024

Spinal diseases, including intervertebral disc degeneration (IDD), ankylosing spondylitis, spinal cord injury and other non‑infectious severely affect the quality of life patients. Current treatments for IDD diseases can only relieve symptoms do not completely cure disease. Therefore, there is an urgent need to explore causes these develop new treatment approaches. Long non‑coding RNA (lncRNA), a form RNA, abundant in diverse sources, has numerous functions, plays important role occurrence development such as IDD. However, mechanism action lncRNAs been fully elucidated, significant challenges remain use therapeutic targets. The present article reviews classification functions lncRNAs, introduces IDD, their potential.

Language: Английский

Citations

1