JOR Spine最新文献

{"title":"Relationship Between Lumbar Multifidus Morphometry and Pain/Disability in Individuals With Chronic Nonspecific Low Back Pain After Considering Demographics, Fear-Avoidance Beliefs, Insomnia, and Spinal Degenerative Changes","authors":"Sabina M. Pinto,&nbsp;Jason P. Y. Cheung,&nbsp;Dino Samartzis,&nbsp;Jaro Karppinen,&nbsp;Yong-Ping Zheng,&nbsp;Marco Y. C. Pang,&nbsp;Maryse Fortin,&nbsp;Arnold Y. L. Wong","doi":"10.1002/jsp2.70071","DOIUrl":"https://doi.org/10.1002/jsp2.70071","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although individuals with chronic low back pain (CLBP) show increased fatty infiltration in the lumbar multifidus muscle (LMM), it remains unclear whether LMM changes are related to clinical outcomes (such as pain and disability) after considering confounders (spinal phenotypes, fear-avoidance beliefs [FABs] and insomnia). This study examined: (1) differences in confounders and LMM characteristics between individuals with and without CLBP; and (2) associations between confounders, LMM parameters, and clinical outcomes in the CLBP group alone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Participants (CLBP = 70 and asymptomatic people = 67) underwent lumbar magnetic resonance imaging. Outcome measures comprised the numeric pain rating scale, the Roland–Morris Disability Questionnaire, the Fear-Avoidance Beliefs Questionnaire (FABQ), and the Insomnia Severity Index (ISI) Scale. LMM morphometry at L3-S1 (cross-sectional area, total volume, and fatty infiltration) was measured using a customized MATLAB program. Spinal phenotypes (disc degeneration, high-intensity zones, Modic changes [MCs], Schmorl's nodes, facet joint degeneration [FJD], and facet tropism [FT]) were scored. The between-group differences were analyzed using linear mixed models and chi-squared/Fisher's exact tests. Univariate and multivariate analyses evaluated associations between clinical outcomes and other outcome measures in the CLBP group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The CLBP group demonstrated more severe disc degeneration and FJD at all levels, and greater FT at L5/S1 than asymptomatic participants (<i>p</i> &lt; 0.05). The average LMM total volume at L3/4 and the percentage of fatty infiltration in LMM in the L3-S1 region were greater in the CLBP group than in asymptomatic counterparts (<i>p</i> &lt; 0.05). The presence of MC at L4 and FJD at L4/5 and L4-S1 was significantly related to pain intensity in the CLBP group. Similarly, FABQ-Work and ISI scores were significantly related to pain intensity (explaining 37% of the variance in pain).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The CLBP group displays more fatty infiltration in the LMM, but their LMM morphometric parameters are unrelated to pain/disability after considering spinal phenotypes, FABs, and insomnia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949789","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":"Intervertebral Lumbar Spine Kinematics in Chronic Low Back Pain Patients Measured Using Biplane Radiography","authors":"William Anderst,&nbsp;C. James Kim,&nbsp;Kevin M. Bell,&nbsp;Tom Gale,&nbsp;Cate Gray,&nbsp;Carol M. Greco,&nbsp;Clarissa LeVasseur,&nbsp;Gina McKernan,&nbsp;Sabreen Megherhi,&nbsp;Charity G. Patterson,&nbsp;Sara R. Piva,&nbsp;Caroline Pellegrini,&nbsp;Michael J. Schneider,&nbsp;Joseph Shoemaker,&nbsp;Patrick Smith,&nbsp;Nam V. Vo,&nbsp;Gwendolyn A. Sowa","doi":"10.1002/jsp2.70069","DOIUrl":"https://doi.org/10.1002/jsp2.70069","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 low back pain (cLBP) presents as a heterogeneous condition, making diagnosis and treatment challenging. Lumbar spine intervertebral kinematics may provide an objective assessment of patients with cLBP that may be used to inform treatment decisions and evaluate the efficacy of interventions. The purpose of this study was to provide a quantitative description of intervertebral motion in the lumbar spine during flexion/extension (F/E) and lateral bending (LB) in individuals with cLBP.&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;Data from 125 individuals is included in this analysis (M: 53; F: 72; &lt;i&gt;n&lt;/i&gt; = 66 &lt; 60 years of age; average BMI: 25.7 ± 3.6 kg/m&lt;sup&gt;2&lt;/sup&gt;). Dynamic biplane radiography (DBR) and a validated volumetric model-based tracking system were used to assess intervertebral motion at every lumbar level (L1-L2 through L5-S1) during active F/E and LB movements in individuals with cLBP. The outcome measures were the intervertebral translation and rotation range of motion (ROM), the contribution of each motion segment to lumbar motion, the anterior–posterior slip per degree of flexion (SPDF), and trial-to-trial repeatability as assessed by the standard deviation in continuous kinematics waveforms over 3 trials of each movement. Outcomes were calculated for the entire group as well as for the subgroups of men, women, individuals less than 60 years of age, and individuals 60 or more years of age.&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 mean intervertebral F/E ROM progressively increased from 6.8° ± 3.1° at the L1-L2 through the L4-L5 motion segments, then decreased from 9.7° ± 5.2° at L4-L5 to 8.4° ± 4.9° at L5-S1. However, substantial variability among individuals was observed, and only 7 participants (5.6%) followed this ROM pattern. The mean intervertebral LB ROM increased from 8.8° ± 3.2° at L1-L2 to 9.1° ± 4.2° at L2-L3 and then progressively decreased from the L2-L3 through the L5-S1 motion segments to 2.7° ± 1.8°. However, only 13 participants (10.4%) followed this ROM pattern. On average, the L1-L2, L2-L3, and L5-S1 motion segments were the main contributors to F/E when the torso was near the upright neutral position. L2-L3, L3-L4, and L4-L5 were the main contributors to midrange flexion and extension, and L3-L4, L4-L5, and L5-S1 were the main contributors to lumbar motion when the trunk was near full flexion. L1-L2 and L2-L3 were the main contributors to lumbar LB near the neutral position and through the midrange. The contributions from L4-L5 and L5-S1 peaked at the neutral position and at maximum bending. SPDF was similar in the L1-L2, L2-L3, and L3-L4 motion segmen","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949817","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":"Mechanisms and Therapeutic Strategies of Macrophage Polarization in Intervertebral Disc Degeneration","authors":"Kaiyuan Zheng,&nbsp;Siyu Wang,&nbsp;Meng Deng,&nbsp;Yaomin Luo,&nbsp;Wen Li,&nbsp;Lianlin Zeng,&nbsp;Yinxu Wang","doi":"10.1002/jsp2.70065","DOIUrl":"https://doi.org/10.1002/jsp2.70065","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IVDD) is a leading cause of low back pain (LBP), contributing significantly to global disability and productivity loss. Its pathogenesis involves complex processes, including inflammation, cellular senescence, angiogenesis, fibrosis, neural ingrowth, and sensitization. Emerging evidence highlights macrophages as central immune regulators infiltrating degenerated discs, with macrophage polarization implicated in IVDD progression. However, the mechanisms linking macrophage polarization to IVDD pathology remain poorly elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive literature review was conducted by searching major databases (PubMed, Web of Science, and Scopus) for studies published in the last decade (2014–2024). Keywords included “intervertebral disc degeneration,” “macrophage polarization,” “inflammation,” “senescence,” and “therapeutic strategies.” Relevant articles were selected, analyzed, and synthesized to evaluate the role of macrophage polarization in IVDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Macrophage polarization dynamically influences IVDD through multiple pathways. Pro-inflammatory M1 macrophages exacerbate disc degeneration by amplifying inflammatory cytokines (e.g., TNF-α, IL-1β), promoting cellular senescence, and stimulating abnormal angiogenesis and neural ingrowth. In contrast, anti-inflammatory M2 macrophages may mitigate degeneration by suppressing inflammation and enhancing tissue repair. Therapeutic strategies targeting macrophage polarization include pharmacological agents (e.g., cytokines, small-molecule inhibitors), biologic therapies, gene editing, and physical interventions. Challenges persist, such as incomplete understanding of polarization triggers, lack of targeted delivery systems, and limited translational success in preclinical models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Macrophage polarization is a pivotal regulator of IVDD pathology, offering promising therapeutic targets. Future research should focus on elucidating polarization mechanisms, optimizing spatiotemporal control of macrophage phenotypes, and developing personalized therapies. Addressing these challenges may advance innovative strategies to halt or reverse IVDD progression, ultimately improving clinical outcomes for LBP patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949818","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":"Human Disc Degeneration Is Accompanied by a Loss of Anterior Annulus Fibrosus Interlamellar Matrix Integrity as Assessed by Peel Tests","authors":"Manmeet S. Dhiman,&nbsp;Mohammed A. Salaam,&nbsp;Taylor J. Bader,&nbsp;Fred Nicholls,&nbsp;W. Bradley Jacobs,&nbsp;Kenneth C. Thomas,&nbsp;Jacques Bouchard,&nbsp;Paul T. Salo,&nbsp;David A. Hart,&nbsp;Ganesh Swamy,&nbsp;Neil A. Duncan","doi":"10.1002/jsp2.70067","DOIUrl":"https://doi.org/10.1002/jsp2.70067","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Disc degeneration (DD) is accompanied by biomechanical changes in the intervertebral discs. The lamellae of the annulus fibrosus (AF) are interconnected through the interlamellar matrix (ILM). The ILM contains interlamellar cross-bridges, connecting the lamellae radially in three dimensions. Weakening of the ILM and the cross-bridges could contribute to delamination between the lamellae, reducing their ability to resist loads and thus contributing to loss of AF integrity associated with the development and progression of degeneration. The objective of the present study was to quantify the differences in interlamellar mechanical properties of fresh AF samples from surgical DD individuals compared to AF samples from non-DD donors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An interlamellar peel test was performed on fresh AF tissue collected from DD surgeries (<i>n</i> = 36) and non-DD organ donors (<i>n</i> = 13). The tissue was peeled at 0.5 mm/s until complete separation. Interlamellar mechanical properties were calculated from the force-displacement curve.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Samples from DD individuals had lower Peel Stiffness (<i>p</i> = 0.001), Peel Strength (<i>p</i> = 0.001), Peel Toughness (<i>p</i> = 0.0009), and Standard Deviation of the Peel Stress (<i>p</i> = 0.02) compared to the tissue from non-DD organ donors. Age had moderate negative correlations with Peel Stiffness (<i>R</i> = −0.59), Peel Strength (<i>R</i> = −0.66), and Peel Toughness (<i>R</i> = −0.69) for non-DD samples only.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>The mechanical integrity of the ILM was determined to be lower in surgical DD individuals compared to non-DD donors. Aging alone may not have affected the results, and rather, loss of the integrity of ILM during disease progression appeared to have significantly contributed to the differences observed. This study provides new mechanical insights into the delamination often observed in the AF of surgical DD individuals. Future biochemical and immunolocalization studies, integrated with mechanical data, will aim to understand the role of collagen and elastin structure and composition in the decreased mechanical integrity of affected tissues.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949819","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":"Diurnal Asymmetric Loading Modulates Cell Phenotype in Intervertebral Disc","authors":"Ying Zhang,&nbsp;Jianbiao Xu,&nbsp;Zhiyu Zhou,&nbsp;R. Geoff Richards,&nbsp;Mauro Alini,&nbsp;Sibylle Grad,&nbsp;Zhen Li","doi":"10.1002/jsp2.70068","DOIUrl":"https://doi.org/10.1002/jsp2.70068","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>This study tested the hypothesis that asymmetric dynamic loading alone or in combination with static loading influences the morphological and biological characteristics of the intervertebral disc (IVD) cells in an ex vivo model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Bovine caudal IVDs were assigned to four groups: (1) Parallel dynamic load (1 h) + free swelling (23 h); (2) Parallel dynamic load (1 h) + static load (23 h); (3) Wedge dynamic load (1 h) + free swelling (23 h); (4) Wedge dynamic load (1 h) + static load (23 h). IVD structure was assessed with measurements of height loss and histological staining. IVD tissue and cellular responses were also measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Diurnal dynamic loading and free swelling recovery could maintain cell viability and the gene expression of organ-cultured discs at their physiological level. Diurnal dynamic loading followed by static loading resulted in a degenerative condition, as indicated by lower cell viability, lower anabolic, and higher catabolic gene expression. Under the dynamic load + free swelling load regime, wedge loading upregulated the ACAN gene expression level in the concave and convex sides of the annulus fibrosus (AF) compared with day 0 healthy control. Under the dynamic load + static loading regime, the MMP1 gene expression showed a trend of increase in the concave and convex sides of the wedge group; the MMP13 gene expression showed a trend of increase in the concave side of the wedge group. The nucleus pulposus (NP) tissue in the wedge group showed a trend of protrusion toward the convex side.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Dynamic loading followed by continuous static loading negatively modulates the phenotype of IVD cells in this organ culture model. Comparable to the free swelling treatment after dynamic loading, physical treatment to reduce the stress on the IVD, even temporarily, may help to prevent the acceleration of deformity and degeneration. These results indicate that asymmetric loading followed by static loading may be used to mimic pathological changes of the IVD in spinal deformity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914384","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":"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}