Jan Ulrich Jansen, Laura Zengerle, Marcel Steiner, Vincenza Sciortino, Marianna Tryfonidou, Hans-Joachim Wilke
Background
Often after large animal experiments in spinal research, the question arises—histology or biomechanics? While biomechanics are essential for informed decisions on the functionality of the therapy being studied, scientists often choose histological analysis alone. For biomechanical testing, for example, flexibility, specimens must be shipped to institutions with special testing equipment, as spine testers are complex and immobile. The specimens must usually be shipped frozen, and, thus, biological and histological investigations are not possible anymore. To allow both biomechanical and biological investigations with the same specimen and, thus, to reduce the number of required animals, the aim of the study was to develop a spine tester that can be shipped worldwide to test on-site.
Methods
The “Spine Tester TO GO” was designed consisting of a frame with three motors that initiate pure moments and rotate the specimen in three motion planes. A load cell and an optical motion tracking system controlled the applied loads and measured range of motion (ROM) and neutral zone (NZ). As a proof of concept, the new machine was validated and compared under real experimental conditions with an existing testing machine already validated employing fresh bovine tail discs CY34 (n = 10).
Results
The new spine tester measured reasonable ROM and NZ from hysteresis curves, and the ROM of the two testing machines formed a high coefficient of determination R2 = 0.986. However, higher ROM results of the new testing machine might be explained by the lower friction of the air bearings, which allowed more translational motion.
Conclusions
The spine tester TO GO now opens up new opportunities for on-site flexibility tests and contributes hereby to the 3R principle by limiting the number of experimental animals needed to obtain full characterization of spine units at the macroscopic, biomechanical, biochemical, and histological level.
背景：脊柱研究中的大型动物实验后往往会出现这样的问题--组织学还是生物力学？虽然生物力学对于决定所研究疗法的功能性至关重要，但科学家们往往只选择组织学分析。要进行生物力学测试，例如柔韧性测试，标本必须运到拥有特殊测试设备的机构，因为脊柱测试仪既复杂又不能移动。标本通常必须冷冻运输，因此无法再进行生物和组织学研究。为了用同一标本进行生物力学和生物学研究，从而减少所需动物的数量，本研究的目的是开发一种可运往世界各地进行现场测试的脊柱测试仪：脊柱测试仪 TO GO "由一个框架和三个电机组成，三个电机可启动纯力矩并在三个运动平面上旋转试样。载荷传感器和光学运动跟踪系统控制施加的载荷，并测量运动范围（ROM）和中立区（NZ）。作为概念验证，在实际实验条件下对新机器进行了验证，并将其与使用新鲜牛尾椎间盘 CY34（n = 10）验证过的现有试验机进行了比较：结果：新型脊柱测试仪通过滞后曲线测量出了合理的 ROM 和 NZ，两台测试仪的 ROM 形成了较高的决定系数 R 2 = 0.986。不过，新试验机的 ROM 结果更高，这可能是因为空气轴承的摩擦力更小，允许更多的平移运动：现在，TO GO脊柱测试仪为现场柔韧性测试提供了新的机会，并通过限制在宏观、生物力学、生物化学和组织学层面获得脊柱单元全面特征所需的实验动物数量，从而为 3R 原则做出了贡献。
{"title":"A novel spine tester TO GO","authors":"Jan Ulrich Jansen, Laura Zengerle, Marcel Steiner, Vincenza Sciortino, Marianna Tryfonidou, Hans-Joachim Wilke","doi":"10.1002/jsp2.70002","DOIUrl":"10.1002/jsp2.70002","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Often after large animal experiments in spinal research, the question arises—histology or biomechanics? While biomechanics are essential for informed decisions on the functionality of the therapy being studied, scientists often choose histological analysis alone. For biomechanical testing, for example, flexibility, specimens must be shipped to institutions with special testing equipment, as spine testers are complex and immobile. The specimens must usually be shipped frozen, and, thus, biological and histological investigations are not possible anymore. To allow both biomechanical and biological investigations with the same specimen and, thus, to reduce the number of required animals, the aim of the study was to develop a spine tester that can be shipped worldwide to test on-site.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The “Spine Tester TO GO” was designed consisting of a frame with three motors that initiate pure moments and rotate the specimen in three motion planes. A load cell and an optical motion tracking system controlled the applied loads and measured range of motion (ROM) and neutral zone (NZ). As a proof of concept, the new machine was validated and compared under real experimental conditions with an existing testing machine already validated employing fresh bovine tail discs CY34 (<i>n</i> = 10).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The new spine tester measured reasonable ROM and NZ from hysteresis curves, and the ROM of the two testing machines formed a high coefficient of determination <i>R</i><sup>2</sup> = 0.986. However, higher ROM results of the new testing machine might be explained by the lower friction of the air bearings, which allowed more translational motion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The spine tester TO GO now opens up new opportunities for on-site flexibility tests and contributes hereby to the 3R principle by limiting the number of experimental animals needed to obtain full characterization of spine units at the macroscopic, biomechanical, biochemical, and histological level.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521957","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}
Daqian Zhou, Tao Liu, Yongliang Mei, Jiale Lv, Kang Cheng, Weiye Cai, Silong Gao, Daru Guo, Xianping Xie, Zongchao Liu
Background
Intervertebral disc degeneration (IVDD) is an age-related orthopedic degenerative disease characterized by recurrent episodes of lower back pain, the pathogenesis of which is not fully understood. This study aimed to identify key biomarkers of IVDD and its causes.
Methods
We acquired three gene expression profiles from the Gene Expression Omnibus (GEO) database, GSE56081, GSE124272, and GSE153761, and used limma fast differential analysis to identify differentially expressed genes (DEGs) between normal and IVDD samples after removing batch effects. We applied weighted gene co-expression network (WGCNA) to identify the key modular genes in GSE124272 and intersected these with DEGs. Next, A protein–protein interaction network (PPI) was constructed, and Cytoscape was used to identify the Top 10 hub genes. Functional enrichment analyses were performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Three key genes were validated using Western Blot (WB) and qRT-PCR. Additionally, we predicted miRNAs involved in hub gene co-regulation and analyzed miRNA microarray data from GSE116726 to identify four differentially expressed miRNAs.
Results
We identified 10 hub genes using bioinformatics analysis, gene function enrichment analysis revealed that they were primarily enriched in pathways, such as the TNF signaling pathway. We chose JUNB, SOCS3, and CEBPB as hub genes and used WB and qRT-PCR to confirm their expression. All three genes were overexpressed in the IVDD model group compared to the control group. Furthermore, we identified four miRNAs involved in the co-regulation of the hub genes using miRNet prediction: mir-191-5p, mir-20a-5p, mir-155-5p, and mir-124-3p. Using limma difference analysis, we discovered that mir-191-5p, mir-20a-5p, and mir-155-5p were all down-regulated and expressed in IVDD samples, but mir-124-3p showed no significant change.
Conclusion
JUNB, SOCS3, and CEBPB were identified as key genes in IVDD, regulated by specific miRNAs, providing potential biomarkers for early diagnosis and therapeutic targets.
{"title":"Identifying critical modules and biomarkers of intervertebral disc degeneration by using weighted gene co-expression network","authors":"Daqian Zhou, Tao Liu, Yongliang Mei, Jiale Lv, Kang Cheng, Weiye Cai, Silong Gao, Daru Guo, Xianping Xie, Zongchao Liu","doi":"10.1002/jsp2.70004","DOIUrl":"https://doi.org/10.1002/jsp2.70004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IVDD) is an age-related orthopedic degenerative disease characterized by recurrent episodes of lower back pain, the pathogenesis of which is not fully understood. This study aimed to identify key biomarkers of IVDD and its causes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We acquired three gene expression profiles from the Gene Expression Omnibus (GEO) database, GSE56081, GSE124272, and GSE153761, and used limma fast differential analysis to identify differentially expressed genes (DEGs) between normal and IVDD samples after removing batch effects. We applied weighted gene co-expression network (WGCNA) to identify the key modular genes in GSE124272 and intersected these with DEGs. Next, A protein–protein interaction network (PPI) was constructed, and Cytoscape was used to identify the Top 10 hub genes. Functional enrichment analyses were performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Three key genes were validated using Western Blot (WB) and qRT-PCR. Additionally, we predicted miRNAs involved in hub gene co-regulation and analyzed miRNA microarray data from GSE116726 to identify four differentially expressed miRNAs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 10 hub genes using bioinformatics analysis, gene function enrichment analysis revealed that they were primarily enriched in pathways, such as the TNF signaling pathway. We chose JUNB, SOCS3, and CEBPB as hub genes and used WB and qRT-PCR to confirm their expression. All three genes were overexpressed in the IVDD model group compared to the control group. Furthermore, we identified four miRNAs involved in the co-regulation of the hub genes using miRNet prediction: mir-191-5p, mir-20a-5p, mir-155-5p, and mir-124-3p. Using limma difference analysis, we discovered that mir-191-5p, mir-20a-5p, and mir-155-5p were all down-regulated and expressed in IVDD samples, but mir-124-3p showed no significant change.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>JUNB, SOCS3, and CEBPB were identified as key genes in IVDD, regulated by specific miRNAs, providing potential biomarkers for early diagnosis and therapeutic targets.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449223","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}
Khaled Aboushaala, Ana V. Chee, Darbaz Adnan, Sheila J. Toro, Harmanjeet Singh, Andrew Savoia, Ekamjeet S. Dhillon, Catherine Yuh, Jake Dourdourekas, Ishani K. Patel, Rajko Vucicevic, Alejandro A. Espinoza-Orias, John T. Martin, Chundo Oh, Ali Keshavarzian, Hanne B. Albert, Jaro Karppinen, Mehmet Kocak, Arnold Y. L. Wong, Edward J. Goldberg, Frank M. Phillips, Matthew W. Colman, Frances M. K. Williams, Jeffrey A. Borgia, Ankur Naqib, Stefan J. Green, Christopher B. Forsyth, Howard S. An, Dino Samartzis
Background
Lumbar degenerative spondylolisthesis (LDS), characterized as degeneration of the intervertebral disc and structural changes of the facet joints, is a condition with varying degrees of instability that may lead to pain, canal stenosis, and subsequent surgical intervention. However, the etiology of LDS remains inconclusive. Gut microbiome dysbiosis may stimulate systemic inflammation in various disorders. However, the role of such dysbiosis upon spine health remains under-studied. The current study assessed the association of gut microbiome dysbiosis in symptomatic patients with or without LDS.
Methods
A cross-sectional analysis within the framework of a prospective study was performed. DNA was extracted from fecal samples collected from adult symptomatic patients with (n = 21) and without LDS (n = 12). Alpha and beta diversity assessed differences in fecal microbial community between groups. Taxon-by-taxon analysis identified microbial features with differential relative abundance between groups. Subject demographics and imaging parameters were also assessed.
Results
There was no significant group differences in age, sex, race, body mass index, smoking/alcohol history, pain profiles, spinopelvic alignment, and Modic changes (p >0.05). LDS subjects had significantly higher disc degeneration severity (p = 0.018) and alpha diversity levels compared to non-LDS subjects (p = 0.002–0.003). Significant differences in gut microbial community structure were observed between groups (p = 0.046). Subjects with LDS exhibited distinct differences at the phylum level, with a significantly higher Firmicutes to Bacteroidota ratio compared to non-LDS (p = 0.003). Differential relative abundance analysis identified six taxa with significant differences between the two groups, with LDS demonstrating an increase in putative pro-inflammatory bacteria (Dialister, CAG-352) and a decrease in anti-inflammatory bacteria (Slackia, Escherichia-Shigella).
Conclusion
This study is the first to report a significant association of gut microbiome dysbiosis and LDS in symptomatic patients, noting pro-inflammatory bacterial taxa. This work provides a foundation for future studies addressing the role of the gut microbiome in association with spine health and disease.
{"title":"Gut microbiome dysbiosis is associated with lumbar degenerative spondylolisthesis in symptomatic patients","authors":"Khaled Aboushaala, Ana V. Chee, Darbaz Adnan, Sheila J. Toro, Harmanjeet Singh, Andrew Savoia, Ekamjeet S. Dhillon, Catherine Yuh, Jake Dourdourekas, Ishani K. Patel, Rajko Vucicevic, Alejandro A. Espinoza-Orias, John T. Martin, Chundo Oh, Ali Keshavarzian, Hanne B. Albert, Jaro Karppinen, Mehmet Kocak, Arnold Y. L. Wong, Edward J. Goldberg, Frank M. Phillips, Matthew W. Colman, Frances M. K. Williams, Jeffrey A. Borgia, Ankur Naqib, Stefan J. Green, Christopher B. Forsyth, Howard S. An, Dino Samartzis","doi":"10.1002/jsp2.70005","DOIUrl":"https://doi.org/10.1002/jsp2.70005","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lumbar degenerative spondylolisthesis (LDS), characterized as degeneration of the intervertebral disc and structural changes of the facet joints, is a condition with varying degrees of instability that may lead to pain, canal stenosis, and subsequent surgical intervention. However, the etiology of LDS remains inconclusive. Gut microbiome dysbiosis may stimulate systemic inflammation in various disorders. However, the role of such dysbiosis upon spine health remains under-studied. The current study assessed the association of gut microbiome dysbiosis in symptomatic patients with or without LDS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cross-sectional analysis within the framework of a prospective study was performed. DNA was extracted from fecal samples collected from adult symptomatic patients with (<i>n</i> = 21) and without LDS (<i>n</i> = 12). Alpha and beta diversity assessed differences in fecal microbial community between groups. Taxon-by-taxon analysis identified microbial features with differential relative abundance between groups. Subject demographics and imaging parameters were also assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There was no significant group differences in age, sex, race, body mass index, smoking/alcohol history, pain profiles, spinopelvic alignment, and Modic changes (<i>p</i> >0.05). LDS subjects had significantly higher disc degeneration severity (<i>p</i> = 0.018) and alpha diversity levels compared to non-LDS subjects (<i>p</i> = 0.002–0.003). Significant differences in gut microbial community structure were observed between groups (<i>p</i> = 0.046). Subjects with LDS exhibited distinct differences at the phylum level, with a significantly higher Firmicutes to Bacteroidota ratio compared to non-LDS (<i>p</i> = 0.003). Differential relative abundance analysis identified six taxa with significant differences between the two groups, with LDS demonstrating an increase in putative pro-inflammatory bacteria (<i>Dialister, CAG-352</i>) and a decrease in anti-inflammatory bacteria (<i>Slackia</i>, <i>Escherichia-Shigella</i>).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study is the first to report a significant association of gut microbiome dysbiosis and LDS in symptomatic patients, noting pro-inflammatory bacterial taxa. This work provides a foundation for future studies addressing the role of the gut microbiome in association with spine health and disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142429819","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}
Intervertebral disc degeneration (IVDD) is a major cause of low back pain (LBP), worsened by chronic inflammatory processes associated with aging. Tumor necrosis factor alpha (Tnf-α) and its receptors, Tnf receptor type 1 (Tnfr1) and Tnf receptor type 2 (Tnfr2), are upregulated in IVDD. However, its pathologic mechanisms remain poorly defined.
Methods
To investigate the role of Tnfr in IVDD, we generated global Tnfr1/2 double knockout (KO) mice and age-matched control C57BL/6 male mice, and analyzed intervertebral disc (IVD)-related phenotypes of both genotypes under physiological conditions, aging, and lumbar spine instability (LSI) model through histological and immunofluorescence analyses and μCT imaging. Expression levels of key extracellular matrix (ECM) proteins in aged and LSI mice, especially markers of cell proliferation and apoptosis, were evaluated in aged (21-month-old) mice.
Results
At 4 months, KO and control mice showed no marked differences of IVDD-related parameters. However, at 21 months of age, the loss of Tnfr expression significantly alleviated IVDD-like phenotypes, including a significant increase in height of the nucleus pulposus (NPs) and reductions of endplates (EPs) porosity and histopathological scores, when compared to controls. Tnfr deficiency promoted anabolic metabolism of the ECM proteins and suppressed ECM catabolism. Tnfr loss largely inhibited hypertrophic differentiation, and, in the meantime, suppressed cell apoptosis and cellular senescence in the annulus fibrosis, NP, and EP tissues without affecting cell proliferation. Similar results were observed in the LSI model, where Tnfr deficiency significantly alleviated IVDD and enhanced ECM anabolic metabolism while suppressing catabolism.
Conclusion
The deletion of Tnfr mitigates age-related and LSI-induced IVDD, as evidenced by preserved IVD structure, and improved ECM integrity. These findings suggest a crucial role of Tnf-α/Tnfr signaling in IVDD pathogenesis in mice. Targeting this pathway may be a novel strategy for IVDD prevention and treatment.
{"title":"Inactivation of Tnf-α/Tnfr signaling attenuates progression of intervertebral disc degeneration in mice","authors":"Chu Tao, Sixiong Lin, Yujia Shi, Weiyuan Gong, Mingjue Chen, Jianglong Li, Peijun Zhang, Qing Yao, Dongyang Qian, Zemin Ling, Guozhi Xiao","doi":"10.1002/jsp2.70006","DOIUrl":"10.1002/jsp2.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IVDD) is a major cause of low back pain (LBP), worsened by chronic inflammatory processes associated with aging. Tumor necrosis factor alpha (Tnf-α) and its receptors, Tnf receptor type 1 (Tnfr1) and Tnf receptor type 2 (Tnfr2), are upregulated in IVDD. However, its pathologic mechanisms remain poorly defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To investigate the role of Tnfr in IVDD, we generated global Tnfr1/2 double knockout (KO) mice and age-matched control C57BL/6 male mice, and analyzed intervertebral disc (IVD)-related phenotypes of both genotypes under physiological conditions, aging, and lumbar spine instability (LSI) model through histological and immunofluorescence analyses and μCT imaging. Expression levels of key extracellular matrix (ECM) proteins in aged and LSI mice, especially markers of cell proliferation and apoptosis, were evaluated in aged (21-month-old) mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At 4 months, KO and control mice showed no marked differences of IVDD-related parameters. However, at 21 months of age, the loss of Tnfr expression significantly alleviated IVDD-like phenotypes, including a significant increase in height of the nucleus pulposus (NPs) and reductions of endplates (EPs) porosity and histopathological scores, when compared to controls. Tnfr deficiency promoted anabolic metabolism of the ECM proteins and suppressed ECM catabolism. Tnfr loss largely inhibited hypertrophic differentiation, and, in the meantime, suppressed cell apoptosis and cellular senescence in the annulus fibrosis, NP, and EP tissues without affecting cell proliferation. Similar results were observed in the LSI model, where Tnfr deficiency significantly alleviated IVDD and enhanced ECM anabolic metabolism while suppressing catabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The deletion of Tnfr mitigates age-related and LSI-induced IVDD, as evidenced by preserved IVD structure, and improved ECM integrity. These findings suggest a crucial role of Tnf-α/Tnfr signaling in IVDD pathogenesis in mice. Targeting this pathway may be a novel strategy for IVDD prevention and treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400307","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}
Lumbar disc herniation (LDH) is a prevalent cause of low back pain. LDH patients commonly experience paraspinal muscle atrophy and fatty infiltration (FI), which further exacerbates the symptoms of low back pain. Magnetic resonance imaging (MRI) is crucial for assessing paraspinal muscle condition. Our study aims to develop a dual-model for automated muscle segmentation and FI annotation on MRI, assisting clinicians evaluate LDH conditions comprehensively.
Methods
The study retrospectively collected data diagnosed with LDH from December 2020 to May 2022. The dataset was split into a 7:3 ratio for training and testing, with an external test set prepared to validate model generalizability. The model's performance was evaluated using average precision (AP), recall and F1 score. The consistency was assessed using the Dice similarity coefficient (DSC) and Cohen's Kappa. The mean absolute percentage error (MAPE) was calculated to assess the error of the model measurements of relative cross-sectional area (rCSA) and FI. Calculate the MAPE of FI measured by threshold algorithms to compare with the model.
Results
A total of 417 patients being evaluated, comprising 216 males and 201 females, with a mean age of 49 ± 15 years. In the internal test set, the muscle segmentation model achieved an overall DSC of 0.92 ± 0.10, recall of 92.60%, and AP of 0.98. The fat annotation model attained a recall of 91.30%, F1 Score of 0.82, and Cohen's Kappa of 0.76. However, there was a decrease on the external test set. For rCSA measurements, except for longissimus (10.89%), the MAPE of other muscles was less than 10%. When comparing the errors of FI for each paraspinal muscle, the MAPE of the model was lower than that of the threshold algorithm.
Conclusion
The models demonstrate outstanding performance, with lower error in FI measurement compared to thresholding algorithms.
{"title":"Deep learning-based structure segmentation and intramuscular fat annotation on lumbar magnetic resonance imaging","authors":"Yefu Xu, Shijie Zheng, Qingyi Tian, Zhuoyan Kou, Wenqing Li, Xinhui Xie, Xiaotao Wu","doi":"10.1002/jsp2.70003","DOIUrl":"https://doi.org/10.1002/jsp2.70003","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lumbar disc herniation (LDH) is a prevalent cause of low back pain. LDH patients commonly experience paraspinal muscle atrophy and fatty infiltration (FI), which further exacerbates the symptoms of low back pain. Magnetic resonance imaging (MRI) is crucial for assessing paraspinal muscle condition. Our study aims to develop a dual-model for automated muscle segmentation and FI annotation on MRI, assisting clinicians evaluate LDH conditions comprehensively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study retrospectively collected data diagnosed with LDH from December 2020 to May 2022. The dataset was split into a 7:3 ratio for training and testing, with an external test set prepared to validate model generalizability. The model's performance was evaluated using average precision (AP), recall and F1 score. The consistency was assessed using the Dice similarity coefficient (DSC) and Cohen's Kappa. The mean absolute percentage error (MAPE) was calculated to assess the error of the model measurements of relative cross-sectional area (rCSA) and FI. Calculate the MAPE of FI measured by threshold algorithms to compare with the model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 417 patients being evaluated, comprising 216 males and 201 females, with a mean age of 49 ± 15 years. In the internal test set, the muscle segmentation model achieved an overall DSC of 0.92 ± 0.10, recall of 92.60%, and AP of 0.98. The fat annotation model attained a recall of 91.30%, F1 Score of 0.82, and Cohen's Kappa of 0.76. However, there was a decrease on the external test set. For rCSA measurements, except for longissimus (10.89%), the MAPE of other muscles was less than 10%. When comparing the errors of FI for each paraspinal muscle, the MAPE of the model was lower than that of the threshold algorithm.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The models demonstrate outstanding performance, with lower error in FI measurement compared to thresholding algorithms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244385","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}
In spinal revision surgery, previous pedicle screws (PS) may need to be replaced with new implants. Failure to accurately identify the brand of PS-based instrumentation preoperatively may increase the risk of perioperative complications. This study aimed to develop and validate an optimal deep learning (DL) model to identify the brand of PS-based instrumentation on plain radiographs of spine (PRS) using anteroposterior (AP) and lateral images.
Methods
A total of 529 patients who received PS-based instrumentation from seven manufacturers were enrolled in this retrospective study. The postoperative PRS were gathered as ground truths. The training, validation, and testing datasets contained 338, 85, and 106 patients, respectively. YOLOv5 was used to crop out the screws' trajectory, and the EfficientNet-b0 model was used to develop single models (AP, Lateral, Merge, and Concatenated) based on the different PRS images. The ensemble models were different combinations of the single models. Primary outcomes were the models' performance in accuracy, sensitivity, precision, F1-score, kappa value, and area under the curve (AUC). Secondary outcomes were the relative performance of models versus human readers and external validation of the DL models.
Results
The Lateral model had the most stable performance among single models. The discriminative performance was improved by the ensemble method. The AP + Lateral ensemble model had the most stable performance, with an accuracy of 0.9434, F1 score of 0.9388, and AUC of 0.9834. The performance of the ensemble models was comparable to that of experienced orthopedic surgeons and superior to that of inexperienced orthopedic surgeons. External validation revealed that the Lat + Concat ensemble model had the best accuracy (0.9412).
Conclusion
The DL models demonstrated stable performance in identifying the brand of PS-based instrumentation based on AP and/or lateral images of PRS, which may assist orthopedic spine surgeons in preoperative revision planning in clinical practice.
{"title":"Development and validation of deep learning models for identifying the brand of pedicle screws on plain spine radiographs","authors":"Yu-Cheng Yao, Cheng-Li Lin, Hung-Hsun Chen, Hsi-Hsien Lin, Wei Hsiung, Shih-Tien Wang, Ying-Chou Sun, Yu-Hsuan Tang, Po-Hsin Chou","doi":"10.1002/jsp2.70001","DOIUrl":"https://doi.org/10.1002/jsp2.70001","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In spinal revision surgery, previous pedicle screws (PS) may need to be replaced with new implants. Failure to accurately identify the brand of PS-based instrumentation preoperatively may increase the risk of perioperative complications. This study aimed to develop and validate an optimal deep learning (DL) model to identify the brand of PS-based instrumentation on plain radiographs of spine (PRS) using anteroposterior (AP) and lateral images.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 529 patients who received PS-based instrumentation from seven manufacturers were enrolled in this retrospective study. The postoperative PRS were gathered as ground truths. The training, validation, and testing datasets contained 338, 85, and 106 patients, respectively. YOLOv5 was used to crop out the screws' trajectory, and the EfficientNet-b0 model was used to develop single models (AP, Lateral, Merge, and Concatenated) based on the different PRS images. The ensemble models were different combinations of the single models. Primary outcomes were the models' performance in accuracy, sensitivity, precision, F1-score, kappa value, and area under the curve (AUC). Secondary outcomes were the relative performance of models versus human readers and external validation of the DL models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The Lateral model had the most stable performance among single models. The discriminative performance was improved by the ensemble method. The AP + Lateral ensemble model had the most stable performance, with an accuracy of 0.9434, F1 score of 0.9388, and AUC of 0.9834. The performance of the ensemble models was comparable to that of experienced orthopedic surgeons and superior to that of inexperienced orthopedic surgeons. External validation revealed that the Lat + Concat ensemble model had the best accuracy (0.9412).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The DL models demonstrated stable performance in identifying the brand of PS-based instrumentation based on AP and/or lateral images of PRS, which may assist orthopedic spine surgeons in preoperative revision planning in clinical practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244386","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}
Milad I. Markhali, John M. Peloquin, Kyle D. Meadows, Harrah R. Newman, Dawn M. Elliott
Background
Magnetic resonance imaging (MRI) noninvasively quantifies disc structure but requires segmentation that is both time intensive and susceptible to human error. Recent advances in neural networks can improve on manual segmentation. The aim of this study was to establish a method for automatic slice-wise segmentation of 3D disc volumes from subjects with a wide range of age and degrees of disc degeneration. A U-Net convolutional neural network was trained to segment 3D T1-weighted spine MRI.
Methods
Lumbar spine MRIs were acquired from 43 subjects (23–83 years old) and manually segmented. A U-Net architecture was trained using the TensorFlow framework. Two rounds of model tuning were performed. The performance of the model was measured using a validation set that did not cross over from the training set. The model version with the best Dice similarity coefficient (DSC) was selected in each tuning round. After model development was complete and a final U-Net model was selected, performance of this model was compared between disc levels and degeneration grades.
Results
Performance of the final model was equivalent to manual segmentation, with a mean DSC = 0.935 ± 0.014 for degeneration grades I–IV. Neither the manual segmentation nor the U-Net model performed as well for grade V disc segmentation. Compared with the baseline model at the beginning of round 1, the best model had fewer filters/parameters (75%), was trained using only slices with at least one disc-labeled pixel, applied contrast stretching to its input images, and used a greater dropout rate.
Conclusion
This study successfully trained a U-Net model for automatic slice-wise segmentation of 3D disc volumes from populations with a wide range of ages and disc degeneration. The final trained model is available to support scientific use.
{"title":"Neural network segmentation of disc volume from magnetic resonance images and the effect of degeneration and spinal level","authors":"Milad I. Markhali, John M. Peloquin, Kyle D. Meadows, Harrah R. Newman, Dawn M. Elliott","doi":"10.1002/jsp2.70000","DOIUrl":"10.1002/jsp2.70000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Magnetic resonance imaging (MRI) noninvasively quantifies disc structure but requires segmentation that is both time intensive and susceptible to human error. Recent advances in neural networks can improve on manual segmentation. The aim of this study was to establish a method for automatic slice-wise segmentation of 3D disc volumes from subjects with a wide range of age and degrees of disc degeneration. A U-Net convolutional neural network was trained to segment 3D T1-weighted spine MRI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Lumbar spine MRIs were acquired from 43 subjects (23–83 years old) and manually segmented. A U-Net architecture was trained using the TensorFlow framework. Two rounds of model tuning were performed. The performance of the model was measured using a validation set that did not cross over from the training set. The model version with the best Dice similarity coefficient (DSC) was selected in each tuning round. After model development was complete and a final U-Net model was selected, performance of this model was compared between disc levels and degeneration grades.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Performance of the final model was equivalent to manual segmentation, with a mean DSC = 0.935 ± 0.014 for degeneration grades I–IV. Neither the manual segmentation nor the U-Net model performed as well for grade V disc segmentation. Compared with the baseline model at the beginning of round 1, the best model had fewer filters/parameters (75%), was trained using only slices with at least one disc-labeled pixel, applied contrast stretching to its input images, and used a greater dropout rate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study successfully trained a U-Net model for automatic slice-wise segmentation of 3D disc volumes from populations with a wide range of ages and disc degeneration. The final trained model is available to support scientific use.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132768","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}
Seyed Mehrad Razavi, Danial Khayatan, Zahra Najafi Arab, Yasamin Hosseini, Maryam Khanahmadi, Saeideh Momtaz, Tannaz Jamialahmadi, Thomas P. Johnston, Amir Hossein Abdolghaffari, Amirhossein Sahebkar
Background
In parallel with population aging, the prevalence of neurological and neurodegenerative diseases has been dramatically increasing over the past few decades. Neurodegenerative diseases reduce the quality of life of patients and impose a high cost on the health system. These slowly progressive diseases can cause functional, perceptual, and behavioral deficits in patients. Therefore, neurodegenerative impairments have always been an interesting subject for scientists and clinicians. One of these diseases is spinal cord injury (SCI). SCI can lead to irreversible damage and is classified into two main subtypes: traumatic and non-traumatic, each with very different pathophysiological features.
Aims
This review aims to gather relevant information about the beneficial effects of curcumin (Cur), with specific emphasis on its anti-inflammatory properties towards spinal cord injury (SCI) patients.
Materials & Methods
The review collates data from extensive in-vitro, in-vivo, and clinical trials documenting the effects of CUR on SCI. It examines the modulation of pathophysiological pathways and regulation of the inflammatory cascades after CUR administration.
Results
Various pathophysiological processes involving the nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NF-kB), and transforming growth factor beta (TGF-β) signaling pathways have been suggested to exacerbate damages resulting from SCI. CUR administration showed to modulate these signaling pathways which lead to attenuation of SCI complications.
Discussion
Anti-inflammatory compounds, particularly CUR, can modulate these pathophysiological pathways and regulate the inflammatory cascades. CUR, a well-known natural product with significant anti-inflammatory effects, has been extensively documented in experimental and clinical trials.
Conclusion
Curcumin's potential to alter key steps in the Nrf2, NF-kB, and TGF-β signaling pathways suggests that it may play a role in attenuating SCI complications.
{"title":"Protective effects of curcumin against spinal cord injury","authors":"Seyed Mehrad Razavi, Danial Khayatan, Zahra Najafi Arab, Yasamin Hosseini, Maryam Khanahmadi, Saeideh Momtaz, Tannaz Jamialahmadi, Thomas P. Johnston, Amir Hossein Abdolghaffari, Amirhossein Sahebkar","doi":"10.1002/jsp2.1364","DOIUrl":"https://doi.org/10.1002/jsp2.1364","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In parallel with population aging, the prevalence of neurological and neurodegenerative diseases has been dramatically increasing over the past few decades. Neurodegenerative diseases reduce the quality of life of patients and impose a high cost on the health system. These slowly progressive diseases can cause functional, perceptual, and behavioral deficits in patients. Therefore, neurodegenerative impairments have always been an interesting subject for scientists and clinicians. One of these diseases is spinal cord injury (SCI). SCI can lead to irreversible damage and is classified into two main subtypes: traumatic and non-traumatic, each with very different pathophysiological features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This review aims to gather relevant information about the beneficial effects of curcumin (Cur), with specific emphasis on its anti-inflammatory properties towards spinal cord injury (SCI) patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials & Methods</h3>\u0000 \u0000 <p>The review collates data from extensive in-vitro, in-vivo, and clinical trials documenting the effects of CUR on SCI. It examines the modulation of pathophysiological pathways and regulation of the inflammatory cascades after CUR administration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Various pathophysiological processes involving the nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NF-kB), and transforming growth factor beta (TGF-β) signaling pathways have been suggested to exacerbate damages resulting from SCI. CUR administration showed to modulate these signaling pathways which lead to attenuation of SCI complications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Anti-inflammatory compounds, particularly CUR, can modulate these pathophysiological pathways and regulate the inflammatory cascades. CUR, a well-known natural product with significant anti-inflammatory effects, has been extensively documented in experimental and clinical trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Curcumin's potential to alter key steps in the Nrf2, NF-kB, and TGF-β signaling pathways suggests that it may play a role in attenuating SCI complications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1364","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980246","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}
<div> <section> <h3> Background</h3> <p>The ligamentum flavum (LF) degeneration is a critical factor in spinal stenosis, leading to nerve compression and pain. Even with new treatment options becoming available, it is vital to have a better understanding of LF degeneration to ensure the effectiveness of these treatments.</p> </section> <section> <h3> Objective</h3> <p>This study aimed to provide insight into LF degeneration by examining the connections between various aspects of LF degeneration, including histology, microstructure, chemical composition, and biomechanics.</p> </section> <section> <h3> Method</h3> <p>We analyzed 30 LF samples from 27 patients with lumbar vertebrae, employing magnetic resonance imaging (MRI) to link lumbar disc degeneration grades with fibrosis levels in the tissue. X-ray diffraction (XRD) analysis assessed microstructural alterations in the LF matrix component due to degeneration progression. Instrumented nanoindentation combined with Raman spectroscopy explored the spatial microbiomechanical and biochemical characteristics of the LF's ventral and dorsal regions.</p> </section> <section> <h3> Results</h3> <p>Our outcomes revealed a clear association between the severity of LF fibrosis grades and increasing LF thickness. XRD analysis showed a rise in crystalline components and hydroxyapatite molecules with progressing degeneration. Raman spectroscopy detected changes in the ratio of phosphate, proteoglycan, and proline/hydroxyproline over the amide I band, indicating alterations in the extracellular matrix composition. Biomechanical testing demonstrated that LF tissue becomes stiffer and less extensible with increasing fibrosis.</p> </section> <section> <h3> Discussion</h3> <p>Notably, the micro-spatial assessment revealed the dorsal side of the LF experiencing more significant mechanical stress, alongside more pronounced biochemical and biomechanical changes compared to the ventral side. Degeneration of the LF involves complex processes that affect tissue histology, chemical composition, and biomechanics. It is crucial to fully understand these changes to develop new and effective treatments for spinal stenosis. These findings can improve diagnostic accuracy, identify potential biomarkers and treatment targets, guide personalized treatment strategies, advance tissue engineering approaches, help make informed clinical decisions, and educate patients about LF degeneration.</p> </section> </di
{"title":"Clinical implications of linking microstructure, spatial biochemical, spatial biomechanical, and radiological features in ligamentum flavum degeneration","authors":"Azril Azril, Kuo-Yuan Huang, Hsin-Yi Liu, Wei-An Liao, Wen-Lung Liu, Jonathan Hobley, Yeau-Ren Jeng","doi":"10.1002/jsp2.1365","DOIUrl":"10.1002/jsp2.1365","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The ligamentum flavum (LF) degeneration is a critical factor in spinal stenosis, leading to nerve compression and pain. Even with new treatment options becoming available, it is vital to have a better understanding of LF degeneration to ensure the effectiveness of these treatments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to provide insight into LF degeneration by examining the connections between various aspects of LF degeneration, including histology, microstructure, chemical composition, and biomechanics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We analyzed 30 LF samples from 27 patients with lumbar vertebrae, employing magnetic resonance imaging (MRI) to link lumbar disc degeneration grades with fibrosis levels in the tissue. X-ray diffraction (XRD) analysis assessed microstructural alterations in the LF matrix component due to degeneration progression. Instrumented nanoindentation combined with Raman spectroscopy explored the spatial microbiomechanical and biochemical characteristics of the LF's ventral and dorsal regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our outcomes revealed a clear association between the severity of LF fibrosis grades and increasing LF thickness. XRD analysis showed a rise in crystalline components and hydroxyapatite molecules with progressing degeneration. Raman spectroscopy detected changes in the ratio of phosphate, proteoglycan, and proline/hydroxyproline over the amide I band, indicating alterations in the extracellular matrix composition. Biomechanical testing demonstrated that LF tissue becomes stiffer and less extensible with increasing fibrosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Notably, the micro-spatial assessment revealed the dorsal side of the LF experiencing more significant mechanical stress, alongside more pronounced biochemical and biomechanical changes compared to the ventral side. Degeneration of the LF involves complex processes that affect tissue histology, chemical composition, and biomechanics. It is crucial to fully understand these changes to develop new and effective treatments for spinal stenosis. These findings can improve diagnostic accuracy, identify potential biomarkers and treatment targets, guide personalized treatment strategies, advance tissue engineering approaches, help make informed clinical decisions, and educate patients about LF degeneration.</p>\u0000 </section>\u0000 </di","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916738","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}
Imke Rudnik-Jansen, Sanda van Kruining Kodele, Laura Creemers, Bert Joosten
Chronic low back pain caused by intervertebral disc (IVD) degeneration, also termed chronic discogenic low back pain (CD-LBP), is one of the most prevalent musculoskeletal diseases. Degenerative processes in the IVD, such as inflammation and extra-cellular matrix breakdown, result in neurotrophin release. Local elevated neurotrophin levels will stimulate sprouting and innervation of sensory neurons. Furthermore, sprouted sensory nerves that are directly connected to adjacent dorsal root ganglia have shown to increase microglia activation, contributing to the maintenance and chronification of pain. Current pain treatments have shown to be insufficient or inadequate for long-term usage. Furthermore, most therapeutic approaches aimed to target the underlying pathogenesis of disc degeneration focus on repair and regeneration and neglect chronic pain. How biomolecular therapies influence the degenerative IVD environment, pain signaling cascades, and innervation and excitability of the sensory neurons often remains unclear. This review addresses the relatively underexplored area of chronic pain treatment for CD-LBP and summarizes effects of therapies aimed for CD-LBP with special emphasis on chronic pain. Approaches based on blocking pro-inflammatory mediators or neurotrophin activity have been shown to hamper neuronal ingrowth into the disc. Furthermore, the tissue regenerative and neuro inhibitory properties of extracellular matrix components or transplanted mesenchymal stem cells are potentially interesting biomolecular approaches to not only block IVD degeneration but also impede pain sensitization. At present, most biomolecular therapies are based on acute IVD degeneration models and thus do not reflect the real clinical chronic pain situation in CD-LBP patients. Future studies should aim at investigating the effects of therapeutic interventions applied in chronic degenerated discs containing established sensory nerve ingrowth. The in-depth understanding of the ramifications from biomolecular therapies on pain (chronification) pathways and pain relief in CD-LBP could help narrow the gap between the pre-clinical bench and clinical bedside for novel CD-LBP therapeutics and optimize pain treatment.
{"title":"Biomolecular therapies for chronic discogenic low back pain: A narrative review","authors":"Imke Rudnik-Jansen, Sanda van Kruining Kodele, Laura Creemers, Bert Joosten","doi":"10.1002/jsp2.1345","DOIUrl":"10.1002/jsp2.1345","url":null,"abstract":"<p>Chronic low back pain caused by intervertebral disc (IVD) degeneration, also termed chronic discogenic low back pain (CD-LBP), is one of the most prevalent musculoskeletal diseases. Degenerative processes in the IVD, such as inflammation and extra-cellular matrix breakdown, result in neurotrophin release. Local elevated neurotrophin levels will stimulate sprouting and innervation of sensory neurons. Furthermore, sprouted sensory nerves that are directly connected to adjacent dorsal root ganglia have shown to increase microglia activation, contributing to the maintenance and chronification of pain. Current pain treatments have shown to be insufficient or inadequate for long-term usage. Furthermore, most therapeutic approaches aimed to target the underlying pathogenesis of disc degeneration focus on repair and regeneration and neglect chronic pain. How biomolecular therapies influence the degenerative IVD environment, pain signaling cascades, and innervation and excitability of the sensory neurons often remains unclear. This review addresses the relatively underexplored area of chronic pain treatment for CD-LBP and summarizes effects of therapies aimed for CD-LBP with special emphasis on chronic pain. Approaches based on blocking pro-inflammatory mediators or neurotrophin activity have been shown to hamper neuronal ingrowth into the disc. Furthermore, the tissue regenerative and neuro inhibitory properties of extracellular matrix components or transplanted mesenchymal stem cells are potentially interesting biomolecular approaches to not only block IVD degeneration but also impede pain sensitization. At present, most biomolecular therapies are based on acute IVD degeneration models and thus do not reflect the real clinical chronic pain situation in CD-LBP patients. Future studies should aim at investigating the effects of therapeutic interventions applied in chronic degenerated discs containing established sensory nerve ingrowth. The in-depth understanding of the ramifications from biomolecular therapies on pain (chronification) pathways and pain relief in CD-LBP could help narrow the gap between the pre-clinical bench and clinical bedside for novel CD-LBP therapeutics and optimize pain treatment.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901879","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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