JOR Spine最新文献

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Plasma Pro- and Anti-Inflammatory Cytokines in an Observational Chronic Low Back Pain Cohort 观察慢性腰痛队列血浆促炎性和抗炎性细胞因子。
IF 3.9 3区 医学
JOR Spine Pub Date : 2025-09-16 DOI: 10.1002/jsp2.70095
Valerio Tonelli Enrico, William Anderst, Kevin M. Bell, J. Paulo Coelho, Jessa Darwin, Anthony Delitto, Carol M. Greco, Joon Y. Lee, Gina P. McKernan, Charity G. Patterson, Sara R. Piva, Michael J. Schneider, Lauren Wilcox, Nam V. Vo, Gwendolyn A. Sowa
{"title":"Plasma Pro- and Anti-Inflammatory Cytokines in an Observational Chronic Low Back Pain Cohort","authors":"Valerio Tonelli Enrico, William Anderst, Kevin M. Bell, J. Paulo Coelho, Jessa Darwin, Anthony Delitto, Carol M. Greco, Joon Y. Lee, Gina P. McKernan, Charity G. Patterson, Sara R. Piva, Michael J. Schneider, Lauren Wilcox, Nam V. Vo, Gwendolyn A. Sowa","doi":"10.1002/jsp2.70095","DOIUrl":"10.1002/jsp2.70095","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic low back pain (cLBP) is a multifactorial condition that can have various contributing factors, including biological, biomechanical, and behavioral. Recent evidence suggests that systemic inflammation may contribute to cLBP, impacting pain sensitivity and individuals' functional status. Circulatory pro- and anti-inflammatory cytokines are widely used to determine individuals' systemic inflammatory status. The University of Pittsburgh Mechanistic Research Center, part of the National Institutes of Health's (NIH) Helping to End Addiction Long-term Initiative, conducted a prospective, observational study to identify phenotypes in a large cohort of individuals with cLBP. The present work reports the quantification of key circulatory cytokines in this cLBP cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 1007 individuals with cLBP were enrolled. Plasma samples were available from 936 participants, and concentrations of pro-inflammatory (IL-6, IFN-γ, TNF, IL-15, Leptin) and anti-inflammatory (IL-1ra, IL-10) cytokines were measured via immunoassays. Pain and functional status were assessed using validated self-reported numeric pain ratings scale and the Oswestry Disability Index. Descriptive statistics of analyzed cytokines were reported across the overall population, stratified by age (< 60 and ≥ 60 years old) and sex, and by pain levels as mild (0–5), moderate (6, 7), and severe (8–10), and ODI, categorized as minimal disability (0%–20%), moderate (21%–40%), and severe disability (> 40%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The values of circulating cytokines assessed in this study aligned with those reported in the literature for other painful inflammatory conditions and, in most cases, exceeded those documented for healthy populations. IL-6, IL-1ra, and Leptin demonstrated higher concentrations with higher pain and disability severity. TNF showed higher concentration in participants with higher disability severity. Concentration levels of IFN-γ, IL-15, and IL-10 exhibited no differences across pain or ODI categories. Notably, TNF levels were higher in older adults (≥ 60 years), whereas Leptin levels were higher in females than in males.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provides a snapshot of key circulating cytokines in a large cLBP cohort, revealing differences in pro- and anti-inflammatory cytokines across pain and disability for the overall population and in sex and age subgroups. Additional longitudinal and mechanistic studies are required to ","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080783","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}
引用次数: 0
MRI-Based Grading Systems for Assessing Lumbar Disc Degeneration: A Scoping Review 评估腰椎间盘退变的mri分级系统:范围综述
IF 3.9 3区 医学
JOR Spine Pub Date : 2025-09-15 DOI: 10.1002/jsp2.70113
Dean Esposito, Benjamin Brown, Mark Jonathan Hancock, Samuel Stuart Graham King, Isaac Gerard Tom Searant, Hazel Jenkins
{"title":"MRI-Based Grading Systems for Assessing Lumbar Disc Degeneration: A Scoping Review","authors":"Dean Esposito,&nbsp;Benjamin Brown,&nbsp;Mark Jonathan Hancock,&nbsp;Samuel Stuart Graham King,&nbsp;Isaac Gerard Tom Searant,&nbsp;Hazel Jenkins","doi":"10.1002/jsp2.70113","DOIUrl":"https://doi.org/10.1002/jsp2.70113","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background Context</h3>\u0000 \u0000 <p>An array of different MRI (magnetic resonance imaging) based grading systems is used to measure disc degeneration (DD) in the lumbar spine. It is currently unclear which grading systems are most commonly used to assess lumbar DD and how these grading systems are applied and reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>The aim of this scoping review was to describe different MRI-based grading systems for DD in the lumbar spine and report which grading systems have been assessed for measurement properties such as reliability, validity, and sensitivity to change.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Study Design/Setting</h3>\u0000 \u0000 <p>Scoping review.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A search was conducted in EMBASE, Medline, and CINAHL for studies related to MRI-based grading systems for DD in the lumbar spine, conducted in living humans. Data were extracted from each study, including the description of the grading system, which levels of the lumbar spine were graded, who graded the degeneration, how the degeneration was scored for analysis, and whether measurement properties such as reliability, validity, and sensitivity to change were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The search identified 569 studies that graded DD. Ninety-three different grading systems were identified, including 63 subjective systems, 25 quantitative systems, and 5 that were unspecified. The Pfirrmann method was used in over 50% of all reports. A range of grading components was used to measure DD, with disc signal intensity (DSI), disc height (DH), and the assessment of the distinctiveness between the annulus and nucleus being most common. Sensitivity to change was rarely assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A large number of DD grading systems were identified in this review, many of which were infrequently used. Variability in methods of assessing DD on MRI and how the MRI data is synthesized may influence reported associations between DD and low back pain (LBP).</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062738","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}
引用次数: 0
Comprehensive Evaluation of Facet Joints Osteoarthritis Radiological Features on Lumbar CT: A Multitask Deep Learning Approach 腰椎CT对小关节骨关节炎放射学特征的综合评价:一种多任务深度学习方法
IF 3.9 3区 医学
JOR Spine Pub Date : 2025-09-11 DOI: 10.1002/jsp2.70115
Yunfei Wang, Ziyang Chen, Junzhang Huang, Qingqing He, Dongming Leng, Lei Yang, Jiaxin Feng, Junjie Lu, Tao Chen, Qianjin Feng, Zhihai Su, Hai Lu, Sheng Lu
{"title":"Comprehensive Evaluation of Facet Joints Osteoarthritis Radiological Features on Lumbar CT: A Multitask Deep Learning Approach","authors":"Yunfei Wang,&nbsp;Ziyang Chen,&nbsp;Junzhang Huang,&nbsp;Qingqing He,&nbsp;Dongming Leng,&nbsp;Lei Yang,&nbsp;Jiaxin Feng,&nbsp;Junjie Lu,&nbsp;Tao Chen,&nbsp;Qianjin Feng,&nbsp;Zhihai Su,&nbsp;Hai Lu,&nbsp;Sheng Lu","doi":"10.1002/jsp2.70115","DOIUrl":"https://doi.org/10.1002/jsp2.70115","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Accurately evaluating the radiological features of facet joint osteoarthritis (FJOA) may help to elucidate its relationship with pain. Multitask deep learning (DL) models have emerged as promising tools for this purpose.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This retrospective study employed a dataset of 13 223 axial CT facet joint (FJ) patches cropped from 1 360 patients across two hospitals. At the image level, the dataset was categorized as training dataset (<i>n</i> = 7430), validation dataset (<i>n</i> = 2000), internal test dataset (<i>n</i> = 1890), and external test dataset (<i>n</i> = 1903). The radiologic features of FJOA were qualitatively assessed using a multitask DL model based on ResNet-18 according to the FJOA grading guidelines proposed by Weishaupt. Two batches of images from each of the internal and external test datasets were used to test the change in readers' assessment accuracy with and without DL assistance, as measured using a paired <i>t</i> test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this study, the accuracy of the model on the internal and external test datasets was 89.8% and 76.6% for joint space narrowing (JSN), 79.6% and 80.2% for osteophytes, 65.5% and 56% for hypertrophy, 88% and 89.6% for subchondral bone erosions, and 82.8% and 89.8% for subchondral cysts. The model's Gwet <i>κ</i> values reach 0.88. When junior readers used the DL model for assistance, the accuracy was significantly improved (<i>p</i> value ranged from &lt; 0.001 to 0.043).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A multitask DL model is a viable method for assessing the severity of radiological features in FJOA, offering support to readers during image evaluation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037839","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}
引用次数: 0
Validation of a Coordinate Optimization Approach for Assessment of In Vivo Intervertebral Kinematics in Patients With Adult Spinal Deformity and Healthy Older Adults 成人脊柱畸形患者和健康老年人体内椎间运动学评估的坐标优化方法的验证
IF 3.9 3区 医学
JOR Spine Pub Date : 2025-09-10 DOI: 10.1002/jsp2.70108
Birgitt Peeters, Mario Keko, Lennart Scheys, Dennis E. Anderson
{"title":"Validation of a Coordinate Optimization Approach for Assessment of In Vivo Intervertebral Kinematics in Patients With Adult Spinal Deformity and Healthy Older Adults","authors":"Birgitt Peeters,&nbsp;Mario Keko,&nbsp;Lennart Scheys,&nbsp;Dennis E. Anderson","doi":"10.1002/jsp2.70108","DOIUrl":"https://doi.org/10.1002/jsp2.70108","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spine kinematics assessment is crucial for understanding intervertebral joint motion, particularly in conditions like spinal deformity, which alters and reduces spinal motion. Estimating spine kinematics in vivo usually relies on kinematic constraints to reduce the degrees of freedom in musculoskeletal models, but they lack standardization and fail to generalize across populations. This study proposes a novel method utilizing coordinate optimization instead of kinematic constraints, aiming to improve the generalizability and accuracy of spine kinematics estimation across different populations and marker protocols.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study used two retrospective datasets: 13 subjects with spinal deformities and 11 healthy individuals. Spine kinematics were estimated by minimizing errors between simulated and experimental marker positions and penalizing large intervertebral joint angles. 3D orientation and position errors against image-based ground truth vertebral orientations and positions and experimental marker positions were calculated and compared for eight different weight settings. The accuracy was further assessed using standard error of measurements (SEM) compared to kinematic constraint methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The best-performing optimization settings resulted in average vertebral orientation errors of 5.1°, 3.2°, and 3.2° for axial rotation, lateral bending, and flexion-extension, respectively, and 3D position errors of 7.7 mm. These values reflect the average of vertebra-specific errors within each subject, further averaged across all subjects in the deformity dataset. Similarly, in the healthy dataset, average 3D marker errors remained below 1 cm, and SEM values remained below 1.3°.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The coordinate optimization method showed robust performance, achieving high accuracy in vertebral orientation and position (deformity) and marker tracking (healthy). This method consistently matched or surpassed state-of-the-art kinematic constraints methods while introducing generalizability across different populations and marker protocols.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022184","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}
引用次数: 0
Advanced Glycation End Products Induce Caudal Disc Degeneration in Ovariectomized Female Rats 晚期糖基化终产物诱导去卵巢雌性大鼠尾盘退变
IF 3.9 3区 医学
JOR Spine Pub Date : 2025-09-09 DOI: 10.1002/jsp2.70114
Xiao Liang, Zhaohui Li, Pengcheng Ren, Ze Gao, Xiaoming Tian, Wei Zhang, Justin Cooper-White, Guobin Liu, Sidong Yang
{"title":"Advanced Glycation End Products Induce Caudal Disc Degeneration in Ovariectomized Female Rats","authors":"Xiao Liang,&nbsp;Zhaohui Li,&nbsp;Pengcheng Ren,&nbsp;Ze Gao,&nbsp;Xiaoming Tian,&nbsp;Wei Zhang,&nbsp;Justin Cooper-White,&nbsp;Guobin Liu,&nbsp;Sidong Yang","doi":"10.1002/jsp2.70114","DOIUrl":"https://doi.org/10.1002/jsp2.70114","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Preclinical animal models are indispensable for the development of new therapeutic strategies and the study of the pathological mechanisms of intervertebral disc (IVD) degeneration (IVDD). This study aims to develop a reliable and reproducible rat model of IVDD by injecting advanced glycation end products (AGEs) into the IVD of ovariectomized rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-eight female Sprague–Dawley rats were allocated into the 31G needle group, vehicle group, 0.5 μg AGEs group, 1 μg AGEs group, 2 μg AGEs group, 4 μg AGEs group, and non-ovariectomy group (<i>n</i> = 4). The coccygeal discs of the 31G needle group were punctured only, while the coccygeal discs of the vehicle group were injected with 1 μL PBS. The coccygeal discs of the AGEs groups underwent injection of AGEs at 0.5, 1, 2, and 4 μg, respectively. The coccygeal discs of the non-ovariectomy group were injected with 2 μg AGEs. Rats in all groups, except for the non-ovariectomy group, underwent bilateral ovariectomy. Two weeks later, the rat caudal models were evaluated using radiological examination, histological staining, and immunohistochemistry (IHC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No signs of IVDD were found by radiological imaging, histology, or IHC in the 31G needle group or the vehicle group. By contrast, in the 0.5, 1, 2, and 4 μg AGEs groups, caudal IVDD was successfully established and the IVDD severity is increasing in a dose-dependent manner. Compared with the 2 μg AGEs group, rats in the non-ovariectomized group showed less IVDD, indicating the protective effect of endogenous estrogen on degenerative IVD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A single injection of AGEs to caudal discs can cause reliable and reproducible IVDD in ovariectomized female rats. Additionally, the endogenous estrogen might have a protective effect on the IVD to mitigate the degeneration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022278","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}
引用次数: 0
A Cross-Tissue Transcriptome-Wide Association Study Identified Susceptibility Genes for Intervertebral Disc Degeneration 一项跨组织转录组关联研究确定了椎间盘退变的易感基因
IF 3.9 3区 医学
JOR Spine Pub Date : 2025-09-07 DOI: 10.1002/jsp2.70109
Li Zhang, Wen Zhao, Hongsheng Yang, Tingting Deng, Yugang Li
{"title":"A Cross-Tissue Transcriptome-Wide Association Study Identified Susceptibility Genes for Intervertebral Disc Degeneration","authors":"Li Zhang,&nbsp;Wen Zhao,&nbsp;Hongsheng Yang,&nbsp;Tingting Deng,&nbsp;Yugang Li","doi":"10.1002/jsp2.70109","DOIUrl":"https://doi.org/10.1002/jsp2.70109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IDD) is a prevalent spinal condition frequently associated with pain and motor impairment, imposing a substantial burden on quality of life. Despite extensive investigations into the genetic predisposition to IDD, the precise pathogenic genes and molecular pathways involved remain inadequately characterized, underscoring the need for continued research to clarify its genetic underpinnings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study leveraged IDD data from the FinnGen R12 cohort and integrated expression quantitative trait loci data across 49 tissues from the Genotype-Tissue Expression version 8 database to perform a cross-tissue transcriptome-wide association study (TWAS). The analytical framework incorporated functional summary-based imputation (FUSION), unified test for molecular signatures (UTMOST), and gene-level analysis via multi-marker genome annotation (MAGMA). To substantiate the findings, Mendelian randomization (MR) and colocalization analyses were subsequently conducted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Through TWAS and MAGMA analyses, 33 susceptibility genes associated with IDD were identified. Subsequent MR and colocalization analyses refined this list to six candidate genes—ADD1, GFPT1, MAPRE3, MSANTD1, SLC30A6, and XBP1—which may contribute to the initiation and progression of IDD by modulating pathways implicated in the endoplasmic reticulum stress response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Six susceptibility genes associated with the risk of IDD were identified in this study, offering novel insights into the genetic architecture and potential pathogenic pathways underpinning the development of IDD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012296","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}
引用次数: 0
TRIM25-Mediated Ubiquitination and Degradation of SOX8 Promotes Ligament Fibroblast Osteogenic Differentiation and Regulates OPLL Progression by Inhibiting OSR2 Transcription trim25介导的泛素化和SOX8降解通过抑制OSR2转录促进韧带成纤维细胞成骨分化并调节OPLL进展
IF 3.9 3区 医学
JOR Spine Pub Date : 2025-09-05 DOI: 10.1002/jsp2.70112
Zhenqiang Wang, Yifan Tang, Changjiang Gu, Minming Lu, Ziheng Wei, Quanwei Zhou, Shengyuan Zhou, Xiongsheng Chen
{"title":"TRIM25-Mediated Ubiquitination and Degradation of SOX8 Promotes Ligament Fibroblast Osteogenic Differentiation and Regulates OPLL Progression by Inhibiting OSR2 Transcription","authors":"Zhenqiang Wang,&nbsp;Yifan Tang,&nbsp;Changjiang Gu,&nbsp;Minming Lu,&nbsp;Ziheng Wei,&nbsp;Quanwei Zhou,&nbsp;Shengyuan Zhou,&nbsp;Xiongsheng Chen","doi":"10.1002/jsp2.70112","DOIUrl":"https://doi.org/10.1002/jsp2.70112","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ossification of the posterior longitudinal ligament (OPLL) is a pathological condition characterized by ectopic ossification of spinal ligaments, primarily driven by abnormal osteogenic differentiation of ligament fibroblasts with stem cell-like properties. The SOX transcription factor family is crucial in regulating cell stemness and differentiation. Among them, SOX8 is known to influence osteoblast differentiation, but its role in OPLL remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>SOX8 expression was analyzed in non-OPLL and OPLL ligament tissues and cells. Its role in osteogenic differentiation was assessed using ALP/Alizarin Red staining, qPCR, Western blotting, and subcutaneous ectopic ossification models in nude mice. Mass spectrometry and co-immunoprecipitation identified SOX8-interacting E3 ubiquitin ligases, with ubiquitination assays assessing their effects on SOX8 stability. RNA-seq, GTRD analysis, and dual-luciferase reporter assays revealed SOX8 target genes. Functional recovery experiments were conducted to explore the role of these interactions in the osteogenic differentiation of ligament fibroblasts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SOX8 expression was downregulated in OPLL ligament tissues and cells. Functional analyses showed that SOX8 inhibits osteogenic differentiation of ligament fibroblasts both in vitro and in vivo. Mechanistically, TRIM25, an E3 ubiquitin ligase, was found to interact with SOX8, promoting its ubiquitination and degradation. Rescue experiments showed that SOX8 knockdown or overexpression reversed the osteogenic effects of TRIM25 knockdown or overexpression in ligament fibroblasts. Additionally, OSR2 was identified as a transcriptional target of SOX8, with SOX8 promoting OSR2 transcription. OSR2 knockdown negated the inhibitory effects of SOX8 overexpression on osteogenic differentiation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SOX8 serves as a critical negative regulator of osteogenic differentiation in ligament fibroblasts. TRIM25 promotes ectopic ossification in OPLL by enhancing SOX8 ubiquitination and degradation, while SOX8 inhibits osteogenic differentiation through transcriptional activation of OSR2. These findings highlight the TRIM25/SOX8/OSR2 axis as a key regulator in OPLL ectopic ossification, suggesting it to be a potential target for non-surgical treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998973","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}
引用次数: 0
Wharton's Jelly Mesenchymal Stromal Cell-Derived Extracellular Vesicles Attenuate Intervertebral Disc Degeneration Under Inflammatory Stress in an In Vitro 3D Culture System 沃顿果冻间充质基质细胞衍生的细胞外囊泡在体外三维培养系统中减轻炎症应激下的椎间盘退变
IF 3.9 3区 医学
JOR Spine Pub Date : 2025-08-20 DOI: 10.1002/jsp2.70106
Veronica Tilotta, Gianluca Vadalà, Giuseppina Di Giacomo, Luca Ambrosio, Claudia Cicione, Fabrizio Russo, Adas Darinskas, Rocco Papalia, Vincenzo Denaro
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引用次数: 0
Quantitative Sensory Testing in an Observational Cohort of Adults With Chronic Low Back Pain 慢性腰痛成人观察队列的定量感觉测试
IF 3.9 3区 医学
JOR Spine Pub Date : 2025-08-19 DOI: 10.1002/jsp2.70103
Michael J. Schneider, Carol M. Greco, Amanda M. Acevedo, Kevin M. Bell, Jessa Darwin, Anthony Delitto, Nathan E. Dodds, John M. Jakicic, Gina P. McKernan, Charity G. Patterson, Paul A. Pilkonis, Sara R. Piva, Gwendolyn A. Sowa, Nam V. Vo, Lan Yu, Ajay D. Wasan
{"title":"Quantitative Sensory Testing in an Observational Cohort of Adults With Chronic Low Back Pain","authors":"Michael J. Schneider,&nbsp;Carol M. Greco,&nbsp;Amanda M. Acevedo,&nbsp;Kevin M. Bell,&nbsp;Jessa Darwin,&nbsp;Anthony Delitto,&nbsp;Nathan E. Dodds,&nbsp;John M. Jakicic,&nbsp;Gina P. McKernan,&nbsp;Charity G. Patterson,&nbsp;Paul A. Pilkonis,&nbsp;Sara R. Piva,&nbsp;Gwendolyn A. Sowa,&nbsp;Nam V. Vo,&nbsp;Lan Yu,&nbsp;Ajay D. Wasan","doi":"10.1002/jsp2.70103","DOIUrl":"https://doi.org/10.1002/jsp2.70103","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Quantitative Sensory Testing (QST), also known as psychophysical testing, includes standardized methods for assessing humans' perceptions of different types of sensory stimuli and their associated pain thresholds. QST results can be used to estimate altered or atypical sensory processing and thus can be useful for determining pain mechanisms such as nociplastic or central nervous system-mediated pain. The University of Pittsburgh Mechanistic Research Center, entitled, “Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB<sup>3</sup>P),” is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. LB<sup>3</sup>P conducted a prospective, observational cohort study to identify phenotypes of over 1000 participants with cLBP. QST was conducted on these participants as part of comprehensive data collection. This article reports on the results of the QST procedures performed at the initial in-person enrollment visit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Four QST procedures were administered to participants of the LB<sup>3</sup>P study at their enrollment visit: (1) Pressure Pain Thresholds (PPT) over the participant-reported site of lumbar pain (paraspinals) and a control site (trapezius) using an analog algometer; (2) Temporal Summation (TS) over the lumbar pain and control sites (forearm) using a Neuropen with a 40-g monofilament; (3) Conditioned Pain Modulation (CPM) using a cold water (5°C) immersion tank; and (4) Cold Water Tolerance time. A subset of LB<sup>3</sup>P participants was excluded from the CPM and cold-water immersion procedures due to medical comorbidities such as cardiovascular disease and diabetic neuropathy. Means and standard deviations (SDs) were calculated from three trials of PPT and TS, two trials of CPM, and one trial of cold-water immersion time. TS was calculated by subtracting the numeric pain scores (0–10 scale) of the first from the 10th pinpricks. CPM was calculated by subtracting the mean trapezius algometer readings during the PPT procedure from those of the trapezius PPT during cold-water immersion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The final cohort of QST participants was 999 adults. The mean/SD of lumbar and trapezius PPTs was 4.6 (2.4) and 4.4 (1.9) kg/cm<sup>2</sup>, respectively. The mean/SD of lumbar and forearm TS was 1.6 (2.0) and 1.2 (1.8). Lingering pain after the 10th pinprick (after-sensations) was reported by 19.3% and 15.6% of participants after a series of 10 pinpricks was applied to the lumbar pain site and control site, respectively. The mean/SD CPM was 0.9 (1.2) with a wide range of CPM values ","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869839","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}
引用次数: 0
Biological Sex Is Under-Reported in Cartilage-Related Preclinical Research: A Cross-Sectional Analysis 生物学性别在软骨相关的临床前研究中被低估:一项横断面分析
IF 3.9 3区 医学
JOR Spine Pub Date : 2025-08-18 DOI: 10.1002/jsp2.70104
Daniele Zuncheddu, Paola Buedo, Martin J. Stoddart, Laura B. Creemers, Sibylle Grad, Marcin Waligora
{"title":"Biological Sex Is Under-Reported in Cartilage-Related Preclinical Research: A Cross-Sectional Analysis","authors":"Daniele Zuncheddu,&nbsp;Paola Buedo,&nbsp;Martin J. Stoddart,&nbsp;Laura B. Creemers,&nbsp;Sibylle Grad,&nbsp;Marcin Waligora","doi":"10.1002/jsp2.70104","DOIUrl":"https://doi.org/10.1002/jsp2.70104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IDD) and osteoarthritis (OA) share many similarities in the molecular processes involved in the onset and progression of these musculoskeletal pathologies. Biological sex is a risk factor for both conditions. Sex bias in orthopedic preclinical research affects knowledge, reproducibility, and translational aspects of basic research. This article aims to provide a comprehensive overview of how donor sex is reported in IDD and OA preclinical research using human or animal samples and in vivo models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a cross-sectional study, searching original articles from journals with the highest impact factor in the field, to determine: (i) whether they report donor sex, and if so, whether they include this data in the analysis; and (ii) whether journals have requirements for sex reporting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our research has four main outcomes. First, donor sex was reported in only 61.9% of the 284 cases examined. Second, among the studies where sex was reported (176), samples were predominantly from only male donors or animals (56%). Moreover, sex was rarely incorporated as a variable in outcome analysis (3.4% of cases). Finally, although 14 out of 23 journals stipulated sex reporting requirements, 37.7% of papers published in these journals failed to report donor sex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results provide evidence for the under-reporting of sample donor sex in OA and IDD research, which may contribute to the poor translation to clinical efficacy and the replication crisis. Our findings could guide journal policies, institutional guidelines for preclinical research, and funder requirements.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861745","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}
引用次数: 0
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