JOR Spine最新文献

{"title":"Identification and Validation of Circadian Rhythm-Related Genes Involved in Intervertebral Disc Degeneration and Analysis of Immune Cell Infiltration via Machine Learning","authors":"Yongbo Zhang,&nbsp;Liuyang Chen,&nbsp;Sheng Yang,&nbsp;Rui Dai,&nbsp;Hua Sun,&nbsp;Liang Zhang","doi":"10.1002/jsp2.70066","DOIUrl":"https://doi.org/10.1002/jsp2.70066","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Low back pain is a significant burden worldwide, and intervertebral disc degeneration (IVDD) is identified as the primary cause. Recent research has emphasized the significant role of circadian rhythms (CRs) and immunity in affecting intervertebral discs (IVD). However, the influence of circadian rhythms and immunity on the mechanism of IVDD remains unclear. This study aimed to identify and validate key rhythm-related genes in IVDD and analyze their correlation with immune cell infiltration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Two gene expression profiles related to IVDD and rhythm-related genes were obtained from the Gene Expression Omnibus and GeneCards databases to identify differentially expressed rhythm-related genes (DERGs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) were conducted to explore the biological functions of these genes. LASSO regression and SVM algorithms were employed to identify hub genes. We subsequently investigated the correlation between hub rhythm-related genes and immune cell infiltration. Finally, nucleus pulposus-derived mesenchymal stem cells (NPMSCs) were isolated from normal and degenerative human IVD tissues. Hub rhythm-related genes expression in NPMSCs was confirmed by real-time quantitative PCR (RT-qPCR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Six hub genes related to CRs (CCND1, FOXO1, FRMD8, NTRK2, PRRT1, and TFPI) were screened out. Immune infiltration analysis revealed that the IVDD group had significantly more M0 macrophages and significantly fewer follicular helper T cells than those of the control group. Specifically, M0 macrophages were significantly associated with FRMD8, PRRT1, and TFPI. T follicular helper cells were significantly associated with FRDM8, FOXO1, and CCND1. We further confirmed that CCND1, FRMD8, NTRK2, and TFPI were dysrhythmic within NPMSCs from degenerated IVD in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Six genes (CCND1, FOXO1, FRMD8, NTRK2, PRRT1 and TFPI) linked to circadian rhythms associated with IVDD progression, together with immunity. The identification of these DEGs may provide new insights for the diagnosis and treatment of IVDD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiological and Anthropometric Factors Associated With Spine Loading Estimates From Imaging-Based Subject-Specific Musculoskeletal Models","authors":"Brett T. Allaire,&nbsp;Fjola Johannesdottir,&nbsp;Mary L. Bouxsein,&nbsp;Dennis E. Anderson","doi":"10.1002/jsp2.70059","DOIUrl":"https://doi.org/10.1002/jsp2.70059","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Subject-specific musculoskeletal models may be used to estimate spine loads that cannot be measured in vivo. Model generation methods may use detailed measurements extracted from medical imaging, but it may be possible to create accurate models without these measurements. We aimed to determine which physiological and anthropometric factors are associated with spine loading and should be accounted for in model creation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We created models of 440 subjects from the Framingham Heart Study Multi-detector CT Study, extracting muscle morphology and spine profile information from CT scans of the trunk. Five lifting activities were simulated, and compressive and shear loading estimates were produced. We performed principal component analysis on the loading data from three locations in the spine, as well as univariate correlations between predictor variables and each principal component (PC). We identified multivariate predictive regression models for each PC and individual loading estimate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A single PC explained 90% of the variability in compressive loading, while four PCs were identified that explained 10%–37% individually, 86% in total, of the variability in shear loading. Univariate analysis showed that body weight, BMI, lean mass, and waist circumference were most associated with the compression PC and first shear PC. Multivariate regression modeling showed predictor variables predicted 94% of the variability in the compression PC, but only 54% in the first shear PC, with body weight having the highest contribution. Additional shear PCs were less predictable. Level- and activity-specific compressive loading was predicted using a limited set of physiological and anthropometric factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This work identifies easily measured characteristics, particularly weight and height, along with sex, associated with subject-specific loading estimates. It suggests that compressive loading, or models to evaluate compressive loading, may be based on a limited set of anthropometric attributes. Shear loading appears more complex and may require additional information not captured in the set of factors we examined.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphatidylethanolamine Protects Nucleus Pulposus Cells From Oxidative Stress-Induced Cellular Senescence and Extracellular Matrix Degradation by Promoting Autophagy","authors":"Yijun Dong,&nbsp;Chuanfu Li,&nbsp;Shuangshuang Tu,&nbsp;Mingkai Liu,&nbsp;Kai Lv,&nbsp;Liqun Duan,&nbsp;Feng Zhang,&nbsp;Haiping Cai,&nbsp;Xi Chen,&nbsp;Wenzhi Zhang","doi":"10.1002/jsp2.70058","DOIUrl":"https://doi.org/10.1002/jsp2.70058","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Intervertebral disc degeneration (IDD) is a type of musculoskeletal system diseases that prevail widely in human society, exerting a substantial economic burden on society. The extensive aggregation of senescent nucleus pulposus (NP) cells within the discs is a significant characteristic of lumbar degenerative alterations. Exploring the underlying mechanisms of NP cell senescence and developing strategies to retard cell senescence are anticipated to become effective approaches for the treatment of IDD.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The study aims to investigate the effects of phosphatidylethanolamine (PE) on autophagic activity, cellular senescence, as well as IDD and dedicated to forging an evidence chain that interconnects IDD, the senescence of NP cells, the autophagic malfunction of NP cells, and the aberrant PE content in NP cells of the advanced-stage group. The resultant outcomes will furnish a theoretical underpinning for the biological prophylaxis and treatment of IDD.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Oxidative stress-induced NP cells senescence is a fundamental characteristic of IDD. To obtain a understanding of the metabolite profile changes in NP cells under stress conditions, Liquid Chromatograph/Mass Spectrometer-based untargeted metabolomics (LC/MS) analysis was utilized in this study. Upon analysis, the distinctive metabolite, PE, which decreased in content in advanced-stage cells, was identified. In this study, Tert-Butyl hydroperoxide (TBHP) was selected as the oxidant to construct an in vitro cellular oxidation model. Methods such as immunofluorescence, immunohistochemistry, Western blotting, and transmission electron microscopy were employed to explore the effects of PE on the senescence of NP cells, the degradation of the extracellular matrix (ECM), and the autophagy of NP cells under stress conditions.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The administration of PE effectively attenuates TBHP-induced cellular senescence and ECM degradation in NP tissue, primarily by stimulating autophagy. Nonetheless, this restorative effect is hindered by chloroquine (CQ), a lysosomal alkalizing agent.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In our study, a series of experiments established a conclusive evidential chain linking IDD, senescence of NP cells, impaired cellular autophagy activity, and abnormal PE content within advanced-stage NP cells. The uni","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage Changes and High-Throughput Sequencing in Aging Mouse Intervertebral Disks","authors":"Wei Wang,&nbsp;Cheng Jiang,&nbsp;Jiong-Hui Chen,&nbsp;Yong-Long Chen,&nbsp;Zhen-Wu Zhang,&nbsp;Zhi-Chao Yang,&nbsp;Jun Li,&nbsp;Xiao-Chuan Li","doi":"10.1002/jsp2.70061","DOIUrl":"https://doi.org/10.1002/jsp2.70061","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disk (IVD) degeneration is associated with lower back pain and aging; however, the mechanisms underlying age-related changes and the changes in macrophage polarization in aging intervertebral disks require further elucidation. The aim of this study was to evaluate changes in macrophages, the differential expression of senescence genes, and their relationship with hub genes in IVDs during aging in mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-eight male wild C57 mice aged 4 weeks were divided into two groups. Four mice per group were selected for high-throughput sequencing and 10 for tail IVD immunohistochemical analysis. Adult and aged mouse IVD specimens were stained with hematoxylin–eosin, Fast Green, and Alcian Blue to determine collagen (Col) 1, Col2, proteoglycan, P16, P21, P53, CD11b, CD86, CD206, IL-1, TGF-β, and IL-4 expression. High-throughput sequencing was performed on adult and aged mouse IVD tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Aged mouse IVDs showed reduced height and marked degeneration, with decreased Col2 and proteoglycan expression and increased Col1 expression. The expression of senescence markers, senescence-associated IL-1, TGF-β, and IL-4, and macrophage-related markers, CD11b, CD86, and CD206, increased markedly with age. High-throughput sequencing revealed 1975 differentially expressed genes in adult and aged mice, with 797 genes showing upregulated expression (top five: <i>Kcna7</i>, <i>Mmp9</i>, <i>Panx3</i>, <i>Myl10</i>, and <i>Bglap</i>) and 1178 showing downregulated expression (top five: <i>Srd5a2</i>, <i>Slc38a5</i>, <i>Gm47283</i>, <i>Npy</i>, and <i>Pcdh8</i>). Gene Ontology and pathway enrichment analyses highlighted aging-related cellular components, biological processes, and metabolic pathways. The identified hub genes included <i>Cox5a</i>, <i>Ndufs6</i>, and <i>Ndufb9</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Disk senescence and reduced height in aged mice are linked to upregulated expression of senescence-associated phenotypes and macrophage polarization markers. These findings suggest that macrophages and differential gene expression play key roles in age-related IVD degeneration, indicating that they can be used as potential targets for therapeutic intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence for a Causal Association Between Human Cytomegalovirus Infection and Chronic Back Pain: A One-Sample Mendelian Randomization Study","authors":"Maryam Kazemi Naeini,&nbsp;Maxim B. Freidin,&nbsp;Isabelle Granville Smith,&nbsp;Stephen Ward,&nbsp;Frances M. K. Williams","doi":"10.1002/jsp2.70063","DOIUrl":"https://doi.org/10.1002/jsp2.70063","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Chronic back pain (CBP) is a major cause of disability globally. While its etiology is multifactorial, specific contributing genetic and environmental factors remain to be discovered. Paraspinal muscle fat has been shown in human and preclinical studies to be related to CBP. One potential risk factor is infection by cytomegalovirus (CMV) because CMV is trophic for fat. CMV may reside in the paraspinal muscle adipose tissue. We set out to test the hypothesis that previous CMV infection is linked to CPB using a one-sample Mendelian randomization (MR).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Method&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The sample comprised 5140 UK Biobank participants with information about CMV serology and CBP status. A one-sample MR based on independent genetic variants predicting CMV positivity was conducted in Northern European participants. To validate the association further, the MR study was repeated using a CMV polygenic risk score (PRS). As a negative control for confounding and spurious causal inference, we used Epstein–Barr virus (EBV) serology, because EBV is another common viral infection but is not trophic for adipose tissue.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A genome-wide association study for CMV seropositivity revealed 86 independent SNPs having p-value &lt; &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;semantics&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mn&gt;2&lt;/mn&gt;\u0000 &lt;mo&gt;×&lt;/mo&gt;\u0000 &lt;msup&gt;\u0000 &lt;mn&gt;10&lt;/mn&gt;\u0000 &lt;mrow&gt;\u0000 &lt;mo&gt;−&lt;/mo&gt;\u0000 &lt;mn&gt;4&lt;/mn&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;/msup&gt;\u0000 &lt;/mrow&gt;\u0000 &lt;annotation&gt;$$ 2times {10}^{-4} $$&lt;/annotation&gt;\u0000 &lt;/semantics&gt;&lt;/math&gt; that have been used to define genetically-predicted categories of CMV infection risk. The CMV predicted categories were found statistically significantly associated with CBP (OR = 1.150; 95% CI: 1.005–1.317, &lt;i&gt;p&lt;/i&gt;-value = 0.043). Stronger significant results were obtained using the PRS for CMV seropositivity (OR = 1.290; 95% CI: 1.133–1.469, &lt;i&gt;p&lt;/i&gt;-value = 12E-4). No such association was seen between EBV and CBP.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our results provide evidence for a causal relationship between CMV infection and CBP. Further investigation is warranted to get insight into the mechanism by which CMV might contribute to the pathogenesis of CBP.&lt;/p&gt;\u0000 ","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Subtypes and Immune Microenvironment Characterization of the Annulus Fibrosus in Intervertebral Disc Degeneration: Insights From Translation Factor-Related Gene Analysis","authors":"Sikuan Zheng,&nbsp;Xiaokun Zhao,&nbsp;Hui Wu,&nbsp;Xuhui Cuan,&nbsp;Xigao Cheng,&nbsp;Dingwen He","doi":"10.1002/jsp2.70064","DOIUrl":"https://doi.org/10.1002/jsp2.70064","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to examine the role of translation factors (TF) in intervertebral disc degeneration (IVDD) and to evaluate their clinical relevance through unsupervised clustering methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Gene expression data were retrieved from the GEO database, and the expression levels of translation factor-related genes (TFGs) were extracted for analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Two distinct molecular clusters were identified based on the differential expression of nine significantly altered TFGs. Immune infiltration was notably higher in Cluster C2 compared to Cluster C1. Subsequently, two gene clusters were identified based on the differentially expressed genes between the clusters. A Sankey diagram illustrated a high degree of consistency between the molecular clusters and the gene clusters. Additionally, four machine learning models were developed and evaluated, with the SVM model being utilized to construct a nomogram for predicting the incidence of IVDD. Validation using external datasets and clinical samples confirmed the low expression of EEF2K, which was further analyzed in a pan-cancer context.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The identification and comprehensive assessment of the two molecular clusters offer significant insights for the classification and treatment of individuals with IVDD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Nicotine Toxicity and Mechanisms of Senescence in Nucleus Pulposus Cells Using Network Toxicology and Molecular Docking Technique","authors":"Chen Jiang,&nbsp;Chao Song,&nbsp;Chaoqi Chen,&nbsp;Baoxin Shen,&nbsp;Lei Yang,&nbsp;Chi Zhang,&nbsp;Fei Liu,&nbsp;Xiaofei Wu,&nbsp;Feng Chen","doi":"10.1002/jsp2.70055","DOIUrl":"https://doi.org/10.1002/jsp2.70055","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Through the use of network toxicology, the research sought to determine whether cellular senescence and associated molecular mechanisms in nicotine-induced intervertebral disc degeneration (IVDD) were potentially harmful.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The primary chemical structure and 105 targets of action of nicotine were determined by using the Swiss Target Prediction, Cell Age, and PubChem databases. 855 IVDD senescence genes were found using the GEO and Cell Age datasets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After additional screening and Cytoscape development, 9 key targets were identified. Additionally, these targets' co-expression pattern analysis and protein interactions were confirmed to be identical. The core targets of nicotine-induced IVDD cellular senescence were found to be primarily enriched in the positive regulation of cell proliferation, telomere shortening, histone acetylation, and cellular senescence-related processes, according to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The KEGG signaling pathway also made it clear that the Apelin signaling route, nicotinate and nicotinamide metabolism, cell cycle, and apoptosis are all strongly linked to nicotine-induced IVDD cellular senescence. We chose four genes associated with the cellular senescence pathway—HDAC1, HDAC4, and NAMPT, MYLK—for molecular docking with the toxic substance nicotine. The findings validated nicotine's strong affinity for the primary targets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>All things considered, the current research indicates that nicotine may contribute to cellular senescence in IVDD via controlling the histone deacetylation process, telomere shortening, the Apelin signaling pathway, and pathways linked to the metabolism of nicotinate and nicotinamide. The theoretical foundation for investigating the molecular mechanisms of nicotine-induced senescence in IVDD is established.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphatidylcholine Ameliorates Palmitic Acid-Induced Lipotoxicity by Facilitating Endoplasmic Reticulum and Mitochondria Contacts in Intervertebral Disc Degeneration","authors":"Shuangshuang Tu,&nbsp;Yijun Dong,&nbsp;Chuanfu Li,&nbsp;Mingxin Jiang,&nbsp;Liqun Duan,&nbsp;Wenzhi Zhang,&nbsp;Xi Chen","doi":"10.1002/jsp2.70062","DOIUrl":"https://doi.org/10.1002/jsp2.70062","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IDD) is a prevalent musculoskeletal disorder with substantial socioeconomic impacts. Despite its high prevalence, the pathogenesis of IDD remains unclear, and effective pharmacological interventions are lacking. This study aimed to investigate metabolic alterations in IDD and explore potential therapeutic targets by analyzing lipotoxicity-related mechanisms in nucleus pulposus (NP) cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Metabolomics and magnetic resonance spectroscopy were utilized to profile metabolic changes in NP tissues from advanced-stage IDD. Transcriptomics and metabolomics integration were performed to identify key regulatory pathways. In vitro experiments using human NP cells exposed to palmitic acid were conducted to evaluate endoplasmic reticulum (ER) stress, mitochondrial dysfunction, lipid droplet accumulation, and senescence. Phosphatidylcholine supplementation was tested for its ability to mitigate lipotoxicity, with ER-mitochondria interactions and mitochondrial oxidation capacity assessed as mechanistic endpoints.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings revealed an abnormal lipotoxic condition in NP cells from advanced-stage IDD. Furthermore, we identified abnormal accumulation of triglycerides and palmitic acid in NP cells from IDD. The palmitic acid accumulation resulted in endoplasmic reticulum stress, mitochondrial damage, lipid droplet accumulation, and senescence of NP cells. By integrating transcriptomics and metabolomics analyses, we discovered that phosphatidylcholine plays a role in regulating palmitic acid-induced lipotoxicity. Notably, phosphatidylcholine level was found to be low in the endoplasmic reticulum and mitochondria of advanced-stage NP cells. Phosphatidylcholine treatment alleviated palmitic acid-induced lipid droplet accumulation and senescence of NP cells by modulating ER-mitochondria contacts and mitochondrial oxidation capacity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Phosphatidylcholine emerges as a potential therapeutic agent to counteract lipotoxic stress by modulating organelle interactions and mitochondrial function. These findings advance our understanding of IDD pathogenesis and provide a novel metabolic target for therapeutic development.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome Data Combined With Mendelian Randomization Analysis Identifies Key Genes Associated With Mitochondria and Programmed Cell Death in Intervertebral Disc Degeneration","authors":"Hongfei Nie,&nbsp;Xiao Hu,&nbsp;Jiaxiao Wang,&nbsp;Jia Wang,&nbsp;Xiaoqian Yu,&nbsp;Jun Li","doi":"10.1002/jsp2.70057","DOIUrl":"https://doi.org/10.1002/jsp2.70057","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IDD) is a major cause of cervical and lumbar diseases, significantly impacting patients' quality of life. Mitochondria and cell death have been implicated in IDD, but the key related genes remain unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Differentially expressed genes (DEGs) between IDD and control samples were identified using GSE70362. Mitochondria-related genes (MRGs) and programmed cell death-related genes (PCDRGs) were intersected with DEGs to find DE-MRGs and DE-PCDRGs. Weighted gene co-expression network analysis (WGCNA) identified key module genes, and the overlap with DEGs revealed candidate genes. Mendelian randomization (MR) analysis was used to determine genes causally linked to IDD. Machine learning and expression validation further refined key genes, which were then used to build a nomogram to predict IDD risk. Additionally, gene set enrichment analysis (GSEA), immune infiltration, and single-cell analysis were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 515 DEGs were intersected with 224 key module genes, yielding 31 candidate genes. Six genes—BCKDHB, BID, TNFAIP6, VRK1, CAB39L, and TMTC1—showed a causal relationship with IDD. BID, TNFAIP6, and TMTC1 were further identified as key genes through machine learning and validation. A nomogram was developed based on these genes. GSEA revealed BID and TMTC1 were enriched in N-glycan biosynthesis, TNFAIP6 and TMTC1 in aminoacyl tRNA biosynthesis, and BID and TMTC1 in ribosomal pathways. Activated dendritic cells, CD56dim natural killer cells, monocytes, and other immune cells were elevated in IDD, with TNFAIP6 strongly correlating with activated dendritic cells. Key genes were expressed at higher levels in degraded samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>BID, TMTC1, and TNFAIP6 were identified as key genes linked to mitochondria and cell death in IDD, offering new insights for diagnosis and treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Significance of MAPK Signaling Pathway in the Diagnosis and Subtype Classification of Intervertebral Disc Degeneration","authors":"Yong Liu,&nbsp;Xueyan Chen,&nbsp;Jingwen Chen,&nbsp;Chao Song,&nbsp;Zhangchao Wei,&nbsp;Zongchao Liu,&nbsp;Fei Liu","doi":"10.1002/jsp2.70060","DOIUrl":"https://doi.org/10.1002/jsp2.70060","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IDD) is a human aging disease related mainly to inflammation, cellular senescence, RNA/DNA methylation, and ECM. The mitogen-activated protein kinase (MAPK) signaling pathway is engaged in multiple biological functions by phosphorylating specific serine and threonine residues on target proteins through phosphorylation cascade effects, but the role and specific mechanisms of the MAPK signaling pathway in IDD are still unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We identified 20 MAPK-related differential genes by differential analysis of the GSE124272 and GSE150408 datasets from the GEO database. To explore the biological functions of these differential genes in humans, we performed GO and KEGG analyses. Additionally, we applied PPI networks, LASSO analysis, the RF algorithm, and the SVM-RFE algorithm to identify core MAPK-related genes. Finally, we conducted further validation using clinical samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We ultimately identified and validated four pivotal MAPK-related genes, namely, KRAS, JUN, RAP1B, and TNF, using clinical samples, and constructed the ROC curves to evaluate the predictive accuracy of the hub genes. A nomogram model was subsequently developed based on these four hub MAPK genes to predict the prevalence of IDD. Based on these four hub genes, we classified IDD patients into two MAP clusters by applying the consensus clustering method and identified 1916 DEGs by analyzing the differences between the two clusters. Further analysis using the same approach allowed us to identify two gene clusters based on these DEGs. We used a PCA algorithm to determine the MAPK score for each sample and discovered that MAPK cluster A and gene cluster A had higher scores, suggesting greater sensitivity to MAPK signaling pathway-associated agents in the subtype. We displayed the differing expression levels of four hub MAPK-related genes across the two clusters and their relationship with immune cell infiltration to highlight the distinctions between clusters A and B.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In summary, four hub MAPK signaling pathway-related genes, KRAS, JUN, RAP1B, and TNF, could be applied to the diagnosis and subtype classification of IDD and benefit the prevention and treatment of IDD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}