Senescence in Intervertebral Disc Degeneration: A Comprehensive Analysis Based on Bioinformatic Strategies DOI Creative Commons
Zijun Zhao, Yining Wang, Zairan Wang

et al.

Immunity Inflammation and Disease, Journal Year: 2024, Volume and Issue: 12(11)

Published: Nov. 1, 2024

ABSTRACT Background Intervertebral disc degeneration (IDD) is a major cause for low back pain. Studies showed the association between senescence and degenerative diseases. Cell can promote occurrence development of diseases through multiple mechanisms including inflammatory stress, oxidative stress nutritional deprivation. The roles senescence‐associated genes (SAGs) remains unknown in IDD. Methods Four differently expressed SAGs were identified as hub using “limma“ package R. We then calculated immune infiltration IDD patients, investigated relation infiltration. Enrichment analysis was performed to explore functions Nomogram LASSO model based on constructed predict risk severe (SD) patients. Subsequently, single cell conducted describe expression pattern intervertebral tissue. Results ASPH, CCND1, IGFBP3 SGK1 SAGs. Further demonstrated that might mediate by regulating pathways. four good performance predicting SD. Single revealed CCND1 mainly nucleus pulposus cells, while epithelial cells. Eleven candidate drugs targeting SAGS predicted patients Comparative Toxicogenomics Database (CDT). PCR immunohistochemical levels higher SD than MD (mild degeneration) Conclusions comprehensive IDD, which their Based SAGs, we established predictive explored potential drugs. These findings provide new understandings SAG mechanism promising therapeutic strategies

Language: Английский

Mitochondrial-Targeted Metal-Phenolic Nanoparticles to Attenuate Intervertebral Disc Degeneration: Alleviating Oxidative Stress and Mitochondrial Dysfunction DOI
Qizhu Chen, Qiuping Qian,

Hongbo Xu

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(12), P. 8885 - 8905

Published: March 11, 2024

As intervertebral disc degeneration (IVDD) proceeds, the dysfunctional mitochondria disrupt viability of nucleus pulposus cells, initiating degradation extracellular matrix. To date, there is a lack effective therapies targeting cells. Here, we synthesized polygallic acid-manganese (PGA-Mn) nanoparticles via self-assembly polymerization gallic acid in an aqueous medium and introduced mitochondrial peptide (TP04) onto using Schiff base linkage, resulting PGA-Mn-TP04 nanoparticles. With size smaller than 50 nm, possesses pH-buffering capacity, avoiding lysosomal confinement selectively accumulating within through electrostatic interactions. The rapid electron exchange between manganese ions enhances redox capability PGA-Mn-TP04, effectively reducing damage caused by reactive oxygen species. Moreover, restores function facilitating fusion minimizing their fission, thereby sustaining vitality In rat IVDD model, maintained height tissue hydration. It offers nonoperative treatment approach for other skeletal muscle diseases from dysfunction, presenting alternative to traditional surgical interventions.

Language: Английский

Citations

27
Molecular mechanism of macrophage polarization regulating the cell senescence of nucleus pulposus during intervertebral disc degeneration DOI
Chao Song, Fei Liu, Xiaofei Wu

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 149, P. 114131 - 114131

Published: Feb. 6, 2025

Language: Английский

Citations

2
Single‐Cell Analysis Integrated With Machine Learning Elucidates the Mechanisms of Nucleus Pulposus Cells Apoptosis in Intervertebral Disc Degeneration and Therapeutic Interventions DOI Creative Commons
Chao Song, Xiaofei Wu, Chaoqi Chen

et al.

JOR Spine, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 20, 2025

ABSTRACT Background The molecular of intervertebral disc degeneration (IVDD) is still unclear. When it comes to treating decoction, traditional Chinese medicine effective. In particular, the Duhuo (Radix Angelicae Biseratae) may be particularly helpful. Purpose To identify nucleus pulposus cells (NPCs) subpopulations and immune clarify mechanism IVDD therapy, offering recommendations for diagnosis treatment. Methods targets from Genecards microarray data biological databases. find key genes pathways underlying IVDD, multiple machine learning techniques were used. associated with NPCs as revealed by single‐cell analysis, immunological infiltration was identified Immune Cell AI. validate which activity affects network pharmacology docking employed. Results process linked like TP53, JUN, PTEN, IL1B, ERBB2, MAPK8, CASP9, PTK2, etc. main mechanisms involved in this are responses, inflammatory factors expression, cellular responses mechanical stimuli, NPC apoptosis. AI discovered a correlation between CD4 naïve, B cell, monocyte, NK, macrophage development IVDD. subtypes namely fibroNPCs, adhesion NPCs, regulatory homeostatic hypertrophic chondrocyte‐like (HT‐CL NPCs), subject mapping. We also found that Osthole, Columbianadin, Bergapten, principal blood entry components Dohuo, have role modulating PTGS1, PARP1, Conclusion exist HT‐CL NPCs. Furthermore, variety cell infiltrates, monocyte macrophage, significant impact on advancement Duhuo, absorb via controlling death

Language: Английский

Citations

1
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
Nanocomposite hydrogel orchestrating multiple modulation of degenerative microenvironment for potential application in intervertebral disc regeneration DOI

Huitong Luo,

Zhipeng Sun, Zetao Wang

et al.

Journal of Material Science and Technology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

1
Bioinformatics‐based discovery of intervertebral disc degeneration biomarkers and immune‐inflammatory infiltrates DOI Creative Commons
Chao Song,

Daqian Zhou,

Kang Cheng

et al.

JOR Spine, Journal Year: 2023, Volume and Issue: 7(1)

Published: Dec. 22, 2023

Intervertebral disc degeneration (IVDD) is a common chronic disease in orthopedics, and its molecular mechanisms are still not well explained.

Language: Английский

Citations

15
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

6
PRDM1 promotes nucleus pulposus cell pyroptosis leading to intervertebral disc degeneration via activating CASP1 transcription DOI Creative Commons
Cheng Yu, Jianjun Li,

Wenhao Kuang

et al.

Cell Biology and Toxicology, Journal Year: 2024, Volume and Issue: 40(1)

Published: Oct. 21, 2024

Intervertebral disc degeneration (IVDD) is a primary contributor to low back pain and poses considerable burden society. However, the molecular mechanisms underlying IVDD remain be elucidated. PR/SET domain 1 (PRDM1) regulates cell proliferation, apoptosis, inflammatory responses in various diseases. Despite these regulatory functions, mechanism of action PRDM1 remains unexplored. In this study, we investigated role progression. The expression nucleus pulposus (NP) tissues NP cells (NPCs) was assessed using western blotting, immunohistochemistry, immunofluorescence. effects on progression were vitro vivo. Mechanistically, mRNA sequencing, chromatin immunoprecipitation, dual-luciferase reporter assays performed confirm that triggered CASP1 transcription. Our study demonstrated for first time substantially upregulated degenerated NPCs. overexpression promoted NPCs pyroptosis by inhibiting mitophagy exacerbating progression, whereas silencing exerted opposite effect. Furthermore, activated transcription, thereby promoting vitro. Notably, reversed To best our knowledge, demonstrate inhibits repressing which may promising new therapeutic target IVDD.

Language: Английский

Citations

5
HIF-1α protects nucleus pulposus cells from oxidative stress-induced mitochondrial impairment through PDK-1 DOI Creative Commons
Zhuochao Liu, Jiancheng Zheng, Tao Ding

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 224, P. 39 - 49

Published: Aug. 10, 2024

The pathogenesis of intervertebral disc degeneration (IVDD) involves complex signaling networks and various effector molecules, our understanding the IVDD is limited. Hypoxia inducible factor-1α (HIF-1α) closely related to IVDD, there excessive oxidative stress concurrent with IVDD. In this study, we found that HIF-1α could protect nucleus pulposus cells from by reversing imbalance between oxidants antioxidants thus mitigating stress-induced mitochondrial impairment. With further exploration, pyruvate dehydrogenase kinase 1 (PDK-1) was involved in protective effect on under stress. We suggested preserve integrity activate glycolysis via PDK-1, addition DCA, a PDK-1 inhibitor, blunt HIF-1α. addition, HIF-1α/PDK-1 regulatory axis also confirmed vivo through knockout mice model. Therefore, propose protects maintaining enriching insight into mechanism against providing novel therapeutic target for treatment

Language: Английский

Citations

4
Antioxidant activities of metal single-atom nanozymes in biomedicine DOI
Qingdong Zeng, Huihai Zhong, Jiahao Liao

et al.

Biomaterials Science, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Nanozymes are a class of nanomaterials with enzyme-like activity that can mimic the catalytic properties natural enzymes. The small size, high activity, and strong stability nanozymes compared to those enzymes allow them not only exist in wide temperature pH range but also maintain complex environments. Recently developed single-atom have metal active sites composed single atom fixed carrier. These atoms act as independent catalytically centers. Metal homogeneous structure suitable coordination environment for stronger specificity than traditional nanozymes. antioxidant ability removing reactive oxygen species (ROS) simulate superoxidase dismutase, catalase, glutathione peroxidase show different effects

Language: Английский

Citations

4