An in‐depth analysis of the immunomodulatory mechanisms of intervertebral disc degeneration

Song, Chao; Cai, Weiye; Liu, Fei; Cheng, Kang; Guo, Daru; Liu, Zongchao

doi:10.1002/jsp2.1233

Cited by 27 publications

(34 citation statements)

References 98 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Through bioinformatic data analysis, we clarified that senescence and apoptosis signaling pathways play an important role in the development of IVDD, and based on our group's previous research and literature, we believe that NPCs are important cells in IVDD. 3,14,30,31 Therefore, we hypothesize that SP1, CASP3, VEGFA, and IL- S7; Figure 9B). We can see from the WB results that CASP3 is different in the model and control groups in protein levels, but the statistical significance is less significant.…”

Section: Results Of Hub Gene Validationmentioning

confidence: 95%

“…IVDD is caused by degeneration and hyalinization of the fibrous ring tissue, water loss in the nucleus pulposus tissue, increased immune cell infiltration, and inflammatory mediators 33 . The majority of current thinking holds that CS and immunological inflammation are inextricably related to the numerous clinical processes associated with IVDD 3,14 . Specifically, CS may accelerate disease progression in IVDD by activating immune‐inflammatory responses through ROS, promoting intervertebral disc ECM breakdown, and apoptosis, as well as by inducing oxidative stress and autophagy 14 .…”

Section: Discussionmentioning

confidence: 99%

“…The immune system response and inflammation are now widely recognized as important drivers of IVDD pathogenesis and progression 3,44,45 . We know that under normal physiological conditions, the nucleus pulposus is the largest immune‐privileged tissue in the body, due to the fact that it is covered by the outer layer of the AF and the upper and lower parts of the CEP in a special enclosed space 46,47 .…”

Section: Discussionmentioning

confidence: 99%

“…Intervertebral disc degeneration (IVDD) is a musculoskeletal degenerative condition associated with aging that lowers people's quality of life and places a greater financial burden on society 1 . The pathogenesis of IVDD is now thought to be primarily caused by cellular senescence (CS) or death of nucleus pulposus cells (NPCs), an imbalance of extracellular matrix (ECM) formation and degradation, and inflammation, oxidative stress, but the precise pathophysiology is not entirely understood 2,3 . Therefore, it is necessary to explore the pathogenesis of IVDD.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Bioinformatics‐based discovery of intervertebral disc degeneration biomarkers and immune‐inflammatory infiltrates

Song,

Zhou,

Cheng

et al. 2023

JOR Spine

Self Cite

View full text Add to dashboard Cite

BackgroundIntervertebral disc degeneration (IVDD) is a common chronic disease in orthopedics, and its molecular mechanisms are still not well explained.AimThis study's objective was to bioinformatics‐based discovery of IVDD biomarkers and immune‐inflammatory infiltrates.Materials and MethodsThe IVDD illness gene collection was gathered from GeneCards, DisGeNet, and gene expression profiles were chosen from the extensive Gene Expression Omnibus database (GSE124272, GSE150408, and GSE153761). The STRING database was used to create a network of protein–protein interactions, while the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases were used for functional enrichment analysis. Using hub genes, the immune cell infiltration between IVDD patient samples and control tissues was examined. Finally, quantitative polymerase chain reaction and Western blot experiments were used to verify the expression of hub genes.ResultsA total of 27 differentially expressed hub genes were identified by bioinformatics. According to GO and KEGG analyses, hub genes were prominent in immunological responses, chemokine‐mediated signaling pathways, and inflammatory responses, with the key signaling pathways engaged in cellular senescence, apoptosis, Th1 and Th2 cell differentiation, and Th17 cell differentiation. Immune cell infiltration research revealed that T cells, lymphocytes, B cells, and NK cells were decreased in IVDD patients while monocytes, neutrophils, and CD8 T cells were increased. The expression levels of the senescence hub genes SP1, VEGFA, IL‐6, and the apoptosis key gene CASP3 were considerably greater in the IVDD model group than in the control group, according to in vitro validation.ConclusionIn conclusion, the cellular senescence signaling pathway, the apoptosis signaling pathway, and associated hub genes play significant roles in the development and progression of IVDD, this finding may help direct future research on the senescence signaling route in IVDD.

show abstract

Section: Results Of Hub Gene Validationmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Bioinformatics‐based discovery of intervertebral disc degeneration biomarkers and immune‐inflammatory infiltrates

Song,

Zhou,

Cheng

et al. 2023

JOR Spine

Self Cite

View full text Add to dashboard Cite

show abstract

“…[40] Many inflammatory factors, including IL-12, TGF-a, IL6, IL1β, IL-21, and IL-23, cause CD4 + Th17 cells to produce IL-17A, which activates downstream signaling pathways leading to IVDD. [41,42] IL-17A alone is not enough to strongly activate the downstream NF-B signaling pathway, according to a search of the KEGG signaling pathway database and literature. As a result, IL-17A and other cytokines like TNF-α and IL-1β costimulate the NF-B signaling pathway and improve the stability of pro-inflammatory cytokine and chemokine gene expression.…”

Section: Idmentioning

confidence: 99%

Exploring the pharmacological mechanism of Duhuo Jisheng Decoction in treating intervertebral disc degeneration based on network pharmacology

et al. 2023

Self Cite

View full text Add to dashboard Cite

Background: The purpose of this study was to examine the mechanism of Duhuo Jisheng Decoction (DHJSD) in the treatment of intervertebral disc degeneration (IVDD). Methods: The active compounds of DHJSD and their corresponding targets were obtained from the TCMSP database. “Intervertebral disc degeneration” was used as a search term in the DisGeNET, GeneCards, Comparative Toxicogenomics Database, and MalaCards database to obtain disease-related targets. Following the discovery of overlapping DHJSD and IVDD targets, enrichment analyses for Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Reactome, and WikiPathways were performed. Cytoscape 3.9.1 was used to build the “DHJSD-Active Ingredients-Target Genes-IVDD” network and protein-protein interaction network, and CytoHubba was used to screen the pivotal genes. Molecular docking confirmed the binding activity of hub genes and key components. Results: The bioinformatic analysis of DHJSD in the treatment of IVDD revealed 209 potential therapeutic gene targets, including 36 important gene targets and 10 of these crucial gene targets. Enrichment analysis of 36 key therapeutic targets showed that the biological processes involved in the Gene Ontology analysis of DHJSD in treating IVDD were mainly cytokine-mediated signaling pathway, inflammatory response, negative regulation of apoptotic process, and vascular endothelial growth factor production. The Kyoto Encyclopedia of Genes and Genomes signaling pathway is mainly involved in TNF signaling pathway, Th17 cell differentiation, IL-17 signaling pathway, and HIF-1 signaling pathway. The Recactome signaling pathway is mainly involved in cytokine signaling in immune system, cellular responses to stress, immune system, cytokines, and inflammatory response. HIF1A and PPARG regulation of glycolysis are mostly involved in the WikiPathways signaling system. The findings demonstrated that to cure IVDD, DHJSD affects the pathogenic processes of inflammation, extracellular matrix, cellular senescence, autophagy, apoptosis, focal death, and proliferation through the aforementioned targets and signaling pathways. The results of molecular docking demonstrated that the protein can be effectively bound by the DHJSD active component. Further evidence was provided for the molecular mechanism through which DHJSD works to treat IVDD. Conclusion: This study uncovers the multi-component, multi-target, and multi-pathway characteristics of DHJSD for the treatment of IVDD, offering fresh perspectives to further investigate the mechanism of DHJSD for the treatment of IVDD.

show abstract

Senescence in Intervertebral Disc Degeneration: A Comprehensive Analysis Based on Bioinformatic Strategies

Zhao,

Wang,

Wang

et al. 2024

Immunity Inflam & Disease

View full text Add to dashboard Cite

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

show abstract

An in‐depth analysis of the immunomodulatory mechanisms of intervertebral disc degeneration

Cited by 27 publications

References 98 publications

Bioinformatics‐based discovery of intervertebral disc degeneration biomarkers and immune‐inflammatory infiltrates

Bioinformatics‐based discovery of intervertebral disc degeneration biomarkers and immune‐inflammatory infiltrates

Exploring the pharmacological mechanism of Duhuo Jisheng Decoction in treating intervertebral disc degeneration based on network pharmacology

Senescence in Intervertebral Disc Degeneration: A Comprehensive Analysis Based on Bioinformatic Strategies

Contact Info

Product

Resources

About