JOR Spine最新文献

{"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}

{"title":"Application and Validation of Semiautomatic Quantification of Immunohistochemically Stained Sections for Low Cellular Tissue Such as Intervertebral Disc Using QuPath","authors":"Andrea Nüesch,&nbsp;Maria Paola Ferri,&nbsp;Christine L. Le Maitre","doi":"10.1002/jsp2.70054","DOIUrl":"https://doi.org/10.1002/jsp2.70054","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Immunohistochemistry (IHC) is a widely used method for localizing and semi-quantifying proteins in tissue samples. Traditional IHC analysis often relies on manually counting 200 cells within a designated area, a time-intensive and subjective process that can compromise reproducibility and accuracy. Advances in digital scanning and bioimage analysis tools, such as the open-source software QuPath, enable semi-automated cell counting, reducing subjectivity and increasing efficiency.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This project developed a QuPath-based script and detailed guide for semi-automatic cell counting, specifically for tissues with low cellularity, such as intervertebral discs and cartilage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>The methodology was validated by demonstrating no significant differences between the manual counting and the semi-automatic quantification (<i>p</i> = 0.783, <i>p</i> = 0.386) while showing a strong correlation between methods for both collagen type II staining (<i>r</i> = 0.9602, <i>p</i> &lt; 0.0001) and N-cadherin staining (<i>r</i> = 0.9044, <i>p</i> = 0.0001). Furthermore, a strong correlation (intraclass correlation coefficient (ICC) single raters = 0.853) between 3 individual raters with varying academic ranks and experiences in IHC analysis was shown using the semi-automatic quantification method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discusssion</h3>\u0000 \u0000 <p>The approach ensures high reproducibility and accuracy, with reduced variability between raters and laboratories. This semi-automated method is particularly suited for tissues with a high extracellular matrix to cell ratio and low cellularity. By minimizing subjectivity and evaluation time, it provides a robust alternative to manual counting, making it ideal for applications where reproducibility and standardization are critical. While the methodology was effective in low-cellularity tissues, its application in other tissue types warrants further exploration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings underscore the potential of QuPath to streamline IHC analysis and enhance inter-laboratory comparability.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565143","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 Cellular Senescence Hub Genes in the Diagnosis and Subtype Classification of a Comprehensive Database of Gene Expression in Intervertebral Disc Degeneration","authors":"Fei Liu,&nbsp;Silong Gao,&nbsp;Ji Yin,&nbsp;Chao Song,&nbsp;Yongliang Mei,&nbsp;Zhaoqiang Wang,&nbsp;Zongchao Liu","doi":"10.1002/jsp2.70050","DOIUrl":"https://doi.org/10.1002/jsp2.70050","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IVDD) is a complex age-related physiological process, with cellular senescence (CS) being a primary contributing factor. However, the precise role of CS and its associated genes in IVDD remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we performed differential expression analysis on the GSE124272 and GSE150408 datasets from the GEO database and identified 53 differentially expressed cellular senescence-related genes (CSRGs). We then conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to explore their functions and associated pathways. We identified hub genes by constructing a protein–protein interaction (PPI) network and further validated these genes using clinical samples. We further explored the functional and prognostic significance of these genes using support vector machine recursive feature elimination (SVM-RFE), random forest (RF), and least absolute shrinkage and selection operator (LASSO) algorithms. We visualized the correlation between the differential expression levels of the four core genes and immune cell infiltration using heat maps and histograms. Finally, we performed graphene oxide enrichment analysis on 297 differentially expressed genes (DEGs) to investigate their role in IVDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We ultimately identified four hub cellular CSRGs DUSP3, MAPKAPK5, SP1, and VEGFA, and further validated their expression using various algorithms and clinical samples. Our results revealed that DUSP3 and SP1 were upregulated in IVDD, while MAPKAPK5 and VEGFA were downregulated. Immune cell infiltration analysis demonstrated that DUSP3 and SP1 were positively correlated with immune cell infiltration levels, whereas VEGFA and MAPKAPK5 were negatively correlated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In summary, CSRGs play an important role in the pathogenesis of IVDD, and our study of the hub gene cluster may guide future therapeutic strategies for IVDD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565144","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":"DeVa (Decay Variance): A Novel Score Calculated via Postprocessing the Changes in Signal Intensity of an Intervertebral Disc in a T2* Multi-Echo Magnetic Resonance Image Can Quantify Painful and Degenerate Lumbar Vertebral Discs","authors":"Stone Sima,&nbsp;Alisha Sial,&nbsp;Suhani Sharma,&nbsp;Dheera Ananthakrishnan,&nbsp;Jeff Kuan,&nbsp;Ashish Diwan","doi":"10.1002/jsp2.70056","DOIUrl":"https://doi.org/10.1002/jsp2.70056","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Low back pain (LBP), a global disability leader, is often linked to intervertebral disc (IVD) degeneration. Traditional diagnostics like T2-weighted MRI provide qualitative but imprecise evaluations. A novel post-processing MRI technique, Decay Variance (DeVa), has shown promise in differentiating degenerate from healthy discs in animal studies. DeVa quantifies IVD degeneration by analyzing variations in signal intensities within each voxel in a T2* 2D FLASH multi-echo MRI sequence. This study aimed to validate DeVa clinically and explore its correlation with pain severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cross-sectional study included 77 chronic LBP patients and 8 controls, who underwent T2-weighted and T2* 2D FLASH MRI. DeVa scores (worst and sum of all discs) were recorded, alongside traditional assessments like disc bulge, stenosis, high-intensity zones, and Pfirrmann grade. Pain severity was measured with a numerical rating scale. Statistical analyses included Pearson correlation, <i>t</i>-tests, and Gardner-Altman plots to evaluate relationships between DeVa scores, degeneration, and pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DeVa scores correlated strongly with Pfirrmann grade (<i>r</i> = 0.692, <i>p</i> &lt; 0.001) and were significantly higher in discs with bulge, stenosis, or high-intensity zones (<i>p</i> &lt; 0.001). Moderate correlations were observed between worst DeVa scores (<i>r</i> = 0.296, <i>p</i> &lt; 0.01), total DeVa scores (<i>r</i> = 0.323, <i>p</i> &lt; 0.005) and pain severity. Patients with chronic LBP without severe degeneration (Pfirrmann ≤ 3 with no stenosis observable on standard MRI) had significantly higher worst (1.38 ± 0.26 vs. 1.10 ± 0.29, <i>p</i> &lt; 0.005) and total (5.39 ± 0.75 vs. 4.65 ± 0.61, <i>p</i> &lt; 0.0.1) DeVa scores compared to controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>DeVa offers a quantitative, noninvasive approach to assessing IVD degeneration, showing strong correlations with disc health and pain. It demonstrates enhanced sensitivity over traditional MRI, enabling the identification of pain-generating discs and informing personalized treatment strategies for chronic LBP. Further validation in larger populations is needed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565145","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":"Ruxolitinib Delays Nucleus Pulposus Cell Senescence in Rat Intervertebral Discs","authors":"Honggang Hao,&nbsp;Weidong Liang,&nbsp;Shuwen Zhang,&nbsp;Xiaoyu Cai,&nbsp;Abulizi Yakefu,&nbsp;Shutao Gao,&nbsp;Chuanhui Xun,&nbsp;Tao Xu,&nbsp;Rui Cao,&nbsp;Weibin Sheng","doi":"10.1002/jsp2.70044","DOIUrl":"https://doi.org/10.1002/jsp2.70044","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration involves aging and senescence of nucleus pulposus cells (NPCs), and JAK/STAT signaling may contribute to this process. The aim of this study was to investigate the therapeutic effect of the JAK2 inhibitor, ruxolitinib, on NPC senescence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Control (third passage), Senescence (sixth passage), JAK inhibitor (ruxolitinib-treated), siRNA-NC (control siRNA-treated), and siRNA-JAK2 (JAK2-targeting siRNA-treated) groups of rat NPCs were established. Cell senescence ratios were determined by β-galactosidase staining and Edu staining was conducted to assess cell proliferation. Cell cycle and apoptosis were analyzed by flow cytometry and Aggrecan and Col II expression detected by immunofluorescence staining. Levels of IL-1β, IL-6, TNF-α, MMP-3, and MMP-13 were detected by ELISA, and p16, p21, p53, p-p53, JAK2, STAT3, p-JAK2, p-STAT3, ADAMTS4, and ADAMTS5 levels were examined by western blot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>More cell senescence was detected by β-galactosidase staining in the Senescence group than in the Control group, while cell proliferation was lower, apoptosis ratio higher, and the percentage of NPCs in G0/G1 phase higher. Levels of senescence-related proteins, including p16, p21, p53, and p-p53, were higher in the Senescence group than the Control group, as were those of IL-1β, IL-6, TNF-α, MMP-3, MMP-13, ADAMTS4, and ADAMTS5. Further, Aggrecan and Col II levels were lower in the Senescence group, while those of JAK2 and STAT3 (JAK2/STAT3 signaling pathway) were higher. Ruxolitinib reversed the changes described above to varying degrees, and the results were supported by those of experiments involving targeted silencing of JAK2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>NPC senescence is characterized by low cell proliferation, a high apoptosis ratio, cell cycle arrest, and generation of senescence-associated secretory phenotypes. NPC senescence can be delayed by inhibiting JAK2/STAT3 signaling using ruxolitinib.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554538","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":"Range of Motion and Neutral Zone of All Human Spinal Motion Segments: A Data Collection of 30 Years of In Vitro Experiments Performed Under Standardized Testing Conditions","authors":"Hans-Joachim Wilke,&nbsp;Annette Kienle,&nbsp;Karin Werner,&nbsp;Christian Liebsch","doi":"10.1002/jsp2.70052","DOIUrl":"https://doi.org/10.1002/jsp2.70052","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spinal flexibility can vary among spinal sections and single motion segments. The purpose of this work was to provide a comprehensive overview of the range of motion (RoM) and neutral zone (NZ) values of all spinal levels collected during 30 years of in vitro experiments under standardized testing conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>RoM and NZ data obtained from in vitro testing of intact human mono- and polysegmental specimens with pure moments of 2.5 Nm for the cervical, 5 Nm for the thoracic, and 7.5 Nm for the lumbar spine were collated from the internal database of the authors' institution. Descriptive statistics were performed with median values and median absolute deviations. Outliers were defined as values beyond twofold standard deviation and excluded from evaluation. Normal distribution was verified using the Shapiro–Wilk test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>RoM and NZ data of <i>N</i> = 1139 functional spinal units were collected with sample sizes ranging from <i>n</i> = 6 to <i>n</i> = 224 per segmental level. The cervical spine was very flexible in flexion/extension and moderately flexible in lateral bending, while in axial rotation, the motion segment C1-C2 was as flexible as the subaxial cervical spine combined. The thoracic spine was the least flexible section in flexion/extension but allowed moderate lateral bending and axial rotation. The rib cage had a strong effect on thoracic spinal flexibility, particularly in axial rotation and at the mid-thoracic spinal levels. The lumbar spine exhibited moderate flexibility in flexion/extension and lateral bending but showed the lowest RoM and NZ in axial rotation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This unique summary of RoM and NZ data, acquired under the same loading conditions in the same spine tester, provides a detailed insight into overall spinal flexibility and will serve as a valid dataset for the validation of in vitro studies and numerical models of the single motion segments of the spine.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554535","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":"Mechanism of Intervertebral Disc Degeneration via the β-Catenin/CCL2 Pathway in Sox9 Conditional Knockout Mice","authors":"Khaled Aboushaala,&nbsp;Ana Chee,&nbsp;Frank Ko,&nbsp;Jad Alkhudari,&nbsp;Saurav Sumughan,&nbsp;Howard S. An,&nbsp;Dino Samartzis,&nbsp;Chun-do Oh","doi":"10.1002/jsp2.70053","DOIUrl":"https://doi.org/10.1002/jsp2.70053","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Degenerative changes in the intervertebral disc (IVD) are known to be a main cause of low back pain (LBP), oftentimes necessitating interventions that may or may not be successful due to a lack of understanding in the degenerative phenotype and its mechanisms. Understanding the molecular mechanisms of disc degeneration can help design new therapies to induce disc regeneration and reduce back pain. This work aimed to understand the effects of conditional deletion of Sox9 in aggrecan-expressing cells on intervertebral disc degeneration and its underlying mechanisms in mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study utilized <i>Agc1-CreERT2;Sox9</i>^{<i>flox/flox</i>} mice to investigate the effects of SOX9 deletion on IVD degeneration and associated pain behaviors. Mice were administered tamoxifen to induce conditional gene deletion of Sox9. Structural and degenerative phenotypes of the spine were assessed by a histological scoring system and micro-computed tomography (microCT). Pain behaviors were evaluated through mechanical allodynia testing and the LABORAS system for spontaneous behavior assessment. Immunohistochemistry identified the expression of proteins of interest, which were further examined by Western blotting. Lastly, quantitative real-time PCR and promoter assays on IVD cells were used to examine inflammatory and signaling pathways induced by Sox9 deletion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Crossing <i>Agc1-CreERT2</i> mice with <i>Sox9</i>^{<i>flox/flox</i>} mice revealed that <i>Sox9</i> conditional deletion (<i>Sox9</i>^<i>cKO</i>) in cartilage tissues causes IVD degeneration and pain behavior. <i>Sox9</i>^<i>cKO</i> mice spines had narrowed intervertebral disc spaces and disorganized IVD tissues. <i>Sox9</i> deletion also increased β-catenin, C-C motif chemokine ligand 2 (CCL2), and Glial cell line-derived neurotrophic factor (GDNF) expression in the IVD, suggesting their roles in disc pain and degeneration and the importance of the β-catenin/CCL2 pathway in these processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Deletion of <i>Sox9</i> in Aggrecan-expressing IVD tissues affects disc degeneration and associated pain behaviors through the β–catenin–CCL2 pathway. Such findings can lead to more targeted, personalized therapeutics in the future to address discogenic origins of LBP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497306","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}