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
Background
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.
Materials and Methods
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 (n = 7430), validation dataset (n = 2000), internal test dataset (n = 1890), and external test dataset (n = 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 t test.
Results
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 κ values reach 0.88. When junior readers used the DL model for assistance, the accuracy was significantly improved (p value ranged from < 0.001 to 0.043).
Conclusion
A multitask DL model is a viable method for assessing the severity of radiological features in FJOA, offering support to readers during image evaluation.
{"title":"Comprehensive Evaluation of Facet Joints Osteoarthritis Radiological Features on Lumbar CT: A Multitask Deep Learning Approach","authors":"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","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 < 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}
Birgitt Peeters, Mario Keko, Lennart Scheys, Dennis E. Anderson
Background
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.
Methods
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.
Results
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°.
Conclusions
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.
{"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, Mario Keko, Lennart Scheys, 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}
Xiao Liang, Zhaohui Li, Pengcheng Ren, Ze Gao, Xiaoming Tian, Wei Zhang, Justin Cooper-White, Guobin Liu, Sidong Yang
Background
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.
Methods
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 (n = 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).
Results
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.
Conclusions
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.
{"title":"Advanced Glycation End Products Induce Caudal Disc Degeneration in Ovariectomized Female Rats","authors":"Xiao Liang, Zhaohui Li, Pengcheng Ren, Ze Gao, Xiaoming Tian, Wei Zhang, Justin Cooper-White, Guobin Liu, 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}
Li Zhang, Wen Zhao, Hongsheng Yang, Tingting Deng, Yugang Li
Background
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.
Methods
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.
Results
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.
Conclusion
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.
{"title":"A Cross-Tissue Transcriptome-Wide Association Study Identified Susceptibility Genes for Intervertebral Disc Degeneration","authors":"Li Zhang, Wen Zhao, Hongsheng Yang, Tingting Deng, 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}
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.
Methods
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.
Results
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.
Conclusions
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.
{"title":"TRIM25-Mediated Ubiquitination and Degradation of SOX8 Promotes Ligament Fibroblast Osteogenic Differentiation and Regulates OPLL Progression by Inhibiting OSR2 Transcription","authors":"Zhenqiang Wang, Yifan Tang, Changjiang Gu, Minming Lu, Ziheng Wei, Quanwei Zhou, Shengyuan Zhou, 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}
This study explores the therapeutic potential of extracellular vesicles (EVs) derived from Wharton's Jelly mesenchymal stem cells in an in vitro 3D model of intervertebral disc degeneration under inflammatory stress. The treatment with WJ-MSC-EVs enhanced nucleus pulposus cell proliferation, viability, and extracellular matrix synthesis while reducing oxidative stress and catabolic gene expression. These results support the promise of WJ-MSC-EVs as a novel, cell-free strategy for disc regeneration in inflammatory conditions.
{"title":"Wharton's Jelly Mesenchymal Stromal Cell-Derived Extracellular Vesicles Attenuate Intervertebral Disc Degeneration Under Inflammatory Stress in an In Vitro 3D Culture System","authors":"Veronica Tilotta, Gianluca Vadalà, Giuseppina Di Giacomo, Luca Ambrosio, Claudia Cicione, Fabrizio Russo, Adas Darinskas, Rocco Papalia, Vincenzo Denaro","doi":"10.1002/jsp2.70106","DOIUrl":"https://doi.org/10.1002/jsp2.70106","url":null,"abstract":"<p>This study explores the therapeutic potential of extracellular vesicles (EVs) derived from Wharton's Jelly mesenchymal stem cells in an in vitro 3D model of intervertebral disc degeneration under inflammatory stress. The treatment with WJ-MSC-EVs enhanced nucleus pulposus cell proliferation, viability, and extracellular matrix synthesis while reducing oxidative stress and catabolic gene expression. These results support the promise of WJ-MSC-EVs as a novel, cell-free strategy for disc regeneration in inflammatory conditions.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869879","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}
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
Background
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 (LB3P),” is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. LB3P 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.
Methods
Four QST procedures were administered to participants of the LB3P 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 LB3P 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.
Results
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/cm2, 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
{"title":"Quantitative Sensory Testing in an Observational Cohort of Adults With Chronic Low Back Pain","authors":"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","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}
Daniele Zuncheddu, Paola Buedo, Martin J. Stoddart, Laura B. Creemers, Sibylle Grad, Marcin Waligora
Background
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.
Methods
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.
Results
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.
Conclusions
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.
{"title":"Biological Sex Is Under-Reported in Cartilage-Related Preclinical Research: A Cross-Sectional Analysis","authors":"Daniele Zuncheddu, Paola Buedo, Martin J. Stoddart, Laura B. Creemers, Sibylle Grad, 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}
James Melrose, Stone Sima, Neha Chopra, Ashish Diwan, Zi Gu
<div> <section> <h3> Background</h3> <p>One of the significant putative causes of low back pain (LBP) is degeneration of the intervertebral disc (IVD). Degenerated discs exhibit loss of proteoglycans, notably aggrecan, leading to mechanical dysfunction and aberrant nerve ingrowth. This pathological innervation results in the proliferation of nociceptive and mechanoreceptive neurons, significantly contributing to persistent pain. A critical therapeutic target is the dorsal root ganglion (DRG), which serves as a key neural hub for nociceptive signaling and neurogenic inflammation. Increased calcium influx through voltage-gated calcium channels within DRG neurons underpins heightened neuronal excitability, facilitating persistent pain transmission. Recent evidence highlights the promising role of bioactive peptides derived from reptilian and insect venoms as potent calcium channel blockers.</p> </section> <section> <h3> Methods</h3> <p>This conceptual review explores published evidence and mechanistic rationale on naturally occurring toxins and venoms as peptide calcium channel blockers for chronic LBP. We considered DRG targeted mechanisms and delivery approaches, including incorporation into biomimetic proteoglycans for localized, sustained intradiscal release, and their use along conventional nerve block procedures.</p> </section> <section> <h3> Results</h3> <p>Venom derived peptide families including ω-conotoxins from cone snail and Tx3-family spider peptides from Phoneutria nigriventer selectively block neuronal calcium channels (notably Ca<sub>v</sub>2.2), thereby reducing the release of neurotransmitters that propogate pain signals. Alongside these antinocicpetive effects, the targeted mechanism of action and directed modalities of these peptides offer a novel therapeutic approach with potential advantages over tradiitonal analgesics, which often present challenges related to tolerance and systemic side effects.</p> </section> <section> <h3> Conclusion</h3> <p>Naturally occurring bioactive peptide calcium channel blockers delivered either directly to the DRG or through a multifaceted therapeutic approach with biomimetic proteoglycans into the IVD or conventional nerve block procedures into the epidural space resents a promising future direction in managing chronic LBP. This approach warrants further pre-clinical and clinical evaluation to clarify clinical utility, potentially transforming pain management paradigms and significantly reducing healthcare burdens associated with chronic spinal disorders.</p> </section> </
{"title":"A Conceptual Review of Naturally Occurring Toxins and Venoms as Peptide Blockers to Combat Chronic Low Back Pain","authors":"James Melrose, Stone Sima, Neha Chopra, Ashish Diwan, Zi Gu","doi":"10.1002/jsp2.70107","DOIUrl":"https://doi.org/10.1002/jsp2.70107","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>One of the significant putative causes of low back pain (LBP) is degeneration of the intervertebral disc (IVD). Degenerated discs exhibit loss of proteoglycans, notably aggrecan, leading to mechanical dysfunction and aberrant nerve ingrowth. This pathological innervation results in the proliferation of nociceptive and mechanoreceptive neurons, significantly contributing to persistent pain. A critical therapeutic target is the dorsal root ganglion (DRG), which serves as a key neural hub for nociceptive signaling and neurogenic inflammation. Increased calcium influx through voltage-gated calcium channels within DRG neurons underpins heightened neuronal excitability, facilitating persistent pain transmission. Recent evidence highlights the promising role of bioactive peptides derived from reptilian and insect venoms as potent calcium channel blockers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This conceptual review explores published evidence and mechanistic rationale on naturally occurring toxins and venoms as peptide calcium channel blockers for chronic LBP. We considered DRG targeted mechanisms and delivery approaches, including incorporation into biomimetic proteoglycans for localized, sustained intradiscal release, and their use along conventional nerve block procedures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Venom derived peptide families including ω-conotoxins from cone snail and Tx3-family spider peptides from Phoneutria nigriventer selectively block neuronal calcium channels (notably Ca<sub>v</sub>2.2), thereby reducing the release of neurotransmitters that propogate pain signals. Alongside these antinocicpetive effects, the targeted mechanism of action and directed modalities of these peptides offer a novel therapeutic approach with potential advantages over tradiitonal analgesics, which often present challenges related to tolerance and systemic side effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Naturally occurring bioactive peptide calcium channel blockers delivered either directly to the DRG or through a multifaceted therapeutic approach with biomimetic proteoglycans into the IVD or conventional nerve block procedures into the epidural space resents a promising future direction in managing chronic LBP. This approach warrants further pre-clinical and clinical evaluation to clarify clinical utility, potentially transforming pain management paradigms and significantly reducing healthcare burdens associated with chronic spinal disorders.</p>\u0000 </section>\u0000 </","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843559","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}
Alaina L. Falck, Erick O. Buko, Kayla L. Chase, Diana Pendleton, Katie McDermott, Olivia Kim, Suhail P. Parvaze, Alexandra R. Armstrong, Susan A. Arnold, Elizabeth W. Bradley, Arin M. Ellingson, Christopher P. Ober, Aaron Rendahl, Casey P. Johnson
Background
Client-owned dogs presenting clinically with intervertebral disc disease (IVDD) are a potential comparative animal model to help advance the understanding of disc degeneration and its treatment. To utilize dog patients as a model, noninvasive imaging techniques are needed that can characterize subtle and progressive changes in disc health in longitudinal and treatment efficacy studies. The purpose of this study was to assess the sensitivity of quantitative MRI techniques in detecting disc degeneration in client-owned, nonchondrodystrophic-breed dogs.
Methods
Thoracolumbar vertebral columns from the donated bodies of 15 dogs without a history of IVDD were imaged at 3T MRI. Quantitative MRI maps (T2, T2*, T1ρ, adiabatic T1ρ, adiabatic T2ρ, and ADC) were acquired axially for 10 discs (T11-T12 to L7-S1), and median values were measured in the nucleus pulposus and annulus fibrosus. Four disc health measures (Pfirrmann grade, histology score, water content, and glycosaminoglycan content) were evaluated for each disc. The quantitative MRI and disc health measures were compared using linear models, and partial correlations (Rpartial) were calculated.
Results
Most dogs had both relatively healthy and degenerated discs as assessed by Pfirrmann grade and histology score. Quantitative MRI values in relatively healthy discs varied greatly between dogs but were similar across disc levels. In the nucleus pulposus, T2 relaxation times were moderately correlated with Pfirrmann grade (Rpartial = −0.62; p < 0.0001), histology score (Rpartial = −0.63; p < 0.0001), and water content (Rpartial = +0.45; p < 0.0001), and weakly correlated with glycosaminoglycan content (Rpartial = +0.31; p = 0.0047). T2, T2*, T1ρ, adiabatic T1ρ, and adiabatic T2ρ had similar relationships to the disc health measures in the nucleus pulposus. No notable relationships were observed with ADC or in the annulus fibrosus.
Conclusions
Quantitative T2, T2*, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation time mapping techniques are similarly related to radiological and histological measures of disc health and water and glycosaminoglycan content in nonchondrodystrophic-breed dogs.
{"title":"Relationship Between Quantitative MRI and Radiological, Histological, and Biochemical Measures of Intervertebral Disc Health in Client-Owned, Nonchondrodystrophic-Breed Dogs","authors":"Alaina L. Falck, Erick O. Buko, Kayla L. Chase, Diana Pendleton, Katie McDermott, Olivia Kim, Suhail P. Parvaze, Alexandra R. Armstrong, Susan A. Arnold, Elizabeth W. Bradley, Arin M. Ellingson, Christopher P. Ober, Aaron Rendahl, Casey P. Johnson","doi":"10.1002/jsp2.70105","DOIUrl":"https://doi.org/10.1002/jsp2.70105","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Client-owned dogs presenting clinically with intervertebral disc disease (IVDD) are a potential comparative animal model to help advance the understanding of disc degeneration and its treatment. To utilize dog patients as a model, noninvasive imaging techniques are needed that can characterize subtle and progressive changes in disc health in longitudinal and treatment efficacy studies. The purpose of this study was to assess the sensitivity of quantitative MRI techniques in detecting disc degeneration in client-owned, nonchondrodystrophic-breed dogs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thoracolumbar vertebral columns from the donated bodies of 15 dogs without a history of IVDD were imaged at 3T MRI. Quantitative MRI maps (T2, T2*, T1ρ, adiabatic T1ρ, adiabatic T2ρ, and ADC) were acquired axially for 10 discs (T11-T12 to L7-S1), and median values were measured in the nucleus pulposus and annulus fibrosus. Four disc health measures (Pfirrmann grade, histology score, water content, and glycosaminoglycan content) were evaluated for each disc. The quantitative MRI and disc health measures were compared using linear models, and partial correlations (<i>R</i><sub>partial</sub>) were calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Most dogs had both relatively healthy and degenerated discs as assessed by Pfirrmann grade and histology score. Quantitative MRI values in relatively healthy discs varied greatly between dogs but were similar across disc levels. In the nucleus pulposus, T2 relaxation times were moderately correlated with Pfirrmann grade (<i>R</i><sub>partial</sub> = −0.62; <i>p</i> < 0.0001), histology score (<i>R</i><sub>partial</sub> = −0.63; <i>p</i> < 0.0001), and water content (<i>R</i><sub>partial</sub> = +0.45; <i>p</i> < 0.0001), and weakly correlated with glycosaminoglycan content (<i>R</i><sub>partial</sub> = +0.31; <i>p</i> = 0.0047). T2, T2*, T1ρ, adiabatic T1ρ, and adiabatic T2ρ had similar relationships to the disc health measures in the nucleus pulposus. No notable relationships were observed with ADC or in the annulus fibrosus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Quantitative T2, T2*, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation time mapping techniques are similarly related to radiological and histological measures of disc health and water and glycosaminoglycan content in nonchondrodystrophic-breed dogs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833055","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}
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