JOR SpinePub Date : 2024-05-27DOI: 10.1002/jsp2.1336
Ryan D. Quarrington, Robert Bauze, Claire F. Jones
{"title":"Kinematics, kinetics, and new insights from a contemporary analysis of the first experiments to produce cervical facet dislocations in the laboratory","authors":"Ryan D. Quarrington, Robert Bauze, Claire F. Jones","doi":"10.1002/jsp2.1336","DOIUrl":"https://doi.org/10.1002/jsp2.1336","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The first experimental study to produce cervical facet dislocation (CFD) in cadaver specimens captured the vertebral motions and axial forces that are important for understanding the injury mechanics. However, these data were not reported in the original manuscript, nor been presented in the limited subsequent studies of experimental CFD. Therefore, the aim of this study was to re-examine the analog data from the first experimental study to determine the local and global spinal motions, and applied axial force, at and preceding CFD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In the original study, quasistatic axial loading was applied to 14 cervical spines by compressing them between two metal plates. Specimens were fixed caudally via a steel spindle positioned within the spinal canal and a bone pin through the inferior-most vertebral body. Global rotation of the occiput was restricted but its anterior translation was unconstrained. The instant of CFD was identified on sagittal cineradiograph films (<i>N</i> = 10), from which global and intervertebral kinematics were also calculated. Corresponding axial force data (<i>N</i> = 6) were extracted, and peak force and force at the instant of injury were determined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CFD occurred in eight specimens, with an intervertebral flexion angle of 34.8 ± 5.6 degrees, and a 3.1 ± 1.9 mm increase in anterior translation, at the injured level. For seven specimens, CFD was produced at the level of transition from upper neck lordosis to lower neck kyphosis. Five specimens with force data underwent CFD at 545 ± 147 N, preceded by a peak axial force (755 ± 233 N) that appeared to coincide with either fracture or soft tissue failure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Re-examining this rich dataset has provided quantitative evidence that small axial compression forces, combined with anterior eccentricity and upper neck extension, can cause flexion and shear in the lower neck, leading to soft tissue rupture and CFD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1336","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Why clinical trials in disc regeneration strive to achieve completion: Insights from publication status and funding sources","authors":"Luca Ambrosio, Giorgia Petrucci, Fabrizio Russo, Claudia Cicione, Rocco Papalia, Gianluca Vadalà, Vincenzo Denaro","doi":"10.1002/jsp2.1329","DOIUrl":"https://doi.org/10.1002/jsp2.1329","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic discogenic low back pain (LBP) poses a significant global burden, yet effective therapeutic interventions directly targeting the underlying degenerative process remain elusive. After demonstrating promising results in preclinical studies, intradiscal injection of cell-based treatments has been increasingly investigated in the clinical setting. However, most clinical trials failed to reach publication, with the few available reports showing only minor improvements. The aim of this study was to analyze the prospective clinical trials registered on ClinicalTrials.gov investigating cell therapies for LBP, with a specific emphasis on identifying critical obstacles hindering study completion, including trial design and funding sources.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic search of prospective clinical trials investigating cell-based treatments for chronic LBP due to intervertebral disc degeneration was performed on ClinicalTrials.gov. Extracted data encompassed study design, recruitment, experimental treatment modalities, investigated outcomes, current status, completion date, publication status, and funding sources. Fisher's exact test assessed associations between categorical variables, while a multiple logistic regression model aimed to identify factors potentially linked to the publication status of the studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our search identified 26 clinical trials. Among these, only 7 (26.9%) were published, and none of the other studies marked as completed reported any results on ClinicalTrials.gov. Fifty percent of included trials were funded by universities, whereas the rest was sponsored by industry (38.5%) or private institutions (11.5%). Experimental treatments primarily involved cell-based or cell-derived products of varying sources and concentrations. Products containing carriers, such as hyaluronic acid or fibrin, were more frequently funded by industry and private organizations (<i>p</i> = 0.0112). No significant differences emerged when comparing published and nonpublished studies based on funding, as well as between publication status and other variables.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Most clinical trials exploring cell-based disc regenerative therapies for chronic LBP have never reached completion, with only a small fraction reporting preliminary data in publications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141096397","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}
JOR SpinePub Date : 2024-05-13DOI: 10.1002/jsp2.1335
Megan Co, Brian Raterman, Brett Klamer, Arunark Kolipaka, Benjamin Walter
{"title":"Nucleus pulposus structure and function assessed in shear using magnetic resonance elastography, quantitative MRI, and rheometry","authors":"Megan Co, Brian Raterman, Brett Klamer, Arunark Kolipaka, Benjamin Walter","doi":"10.1002/jsp2.1335","DOIUrl":"https://doi.org/10.1002/jsp2.1335","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In vivo quantification of the structure–function relationship of the intervertebral disc (IVD) via quantitative MRI has the potential to aid objective stratification of disease and evaluation of restorative therapies. Magnetic resonance elastography (MRE) is an imaging technique that assesses tissue shear properties and combined with quantitative MRI metrics reflective of composition can inform structure–function of the IVD. The objectives of this study were to (1) compare MRE- and rheometry-derived shear modulus in agarose gels and nucleus pulposus (NP) tissue and (2) correlate MRE and rheological measures of NP tissue with composition and quantitative MRI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>MRE and MRI assessment (i.e., T1ρ and T2 mapping) of agarose samples (2%, 3%, and 4% (w/v); <i>n</i> = 3–4/%) and of bovine caudal IVDs after equilibrium dialysis in 5% or 25% PEG (<i>n</i> = 13/PEG%) was conducted. Subsequently, agarose and NP tissue underwent torsional mechanical testing consisting of a frequency sweep from 1 to 100 Hz at a rotational strain of 0.05%. NP tissue was additionally evaluated under creep and stress relaxation conditions. Linear mixed-effects models and univariate regression analyses evaluated the effects of testing method, %agarose or %PEG, and frequency, as well as correlations between parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MRE- and rheometry-derived shear moduli were greater at 100 Hz than at 80 Hz in all agarose and NP tissue samples. Additionally, all samples with lower water content had higher complex shear moduli. There was a significant correlation between MRE- and rheometry-derived modulus values for homogenous agarose samples. T1ρ and T2 relaxation times for agarose and tissue were negatively correlated with complex shear modulus derived from both techniques. For NP tissue, shear modulus was positively correlated with GAG/wet-weight and negatively correlated with %water content.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This work demonstrates that MRE can assess hydration-induced changes in IVD shear properties and further highlights the structure–function relationship between composition and shear mechanical behaviors of NP tissue.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1335","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140914790","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}
JOR SpinePub Date : 2024-05-06DOI: 10.1002/jsp2.1334
Seth S. Leopold, Robert N. Hensinger, Andrew J. Schoenfeld, Marc Swiontkowski, Michael J. Rossi, Kimberly J. Templeton, Sex and Gender Research in Orthopaedic Journals Group
{"title":"Improving how orthopedic journals report research outcomes based on sex and gender","authors":"Seth S. Leopold, Robert N. Hensinger, Andrew J. Schoenfeld, Marc Swiontkowski, Michael J. Rossi, Kimberly J. Templeton, Sex and Gender Research in Orthopaedic Journals Group","doi":"10.1002/jsp2.1334","DOIUrl":"https://doi.org/10.1002/jsp2.1334","url":null,"abstract":"<p>Sex-based differences in cell biology, tissue function, and anatomy impact disease risk, presentation, and treatment outcomes,<span><sup>1</sup></span> including in musculoskeletal care.<span><sup>2-4</sup></span> As such, these differences should influence how orthopedic surgeons and other healthcare professionals conduct research and provide care for patients who have musculoskeletal disease and injury. In addition, gender roles influence interactions with people who conduct research and healthcare professionals, as well as the likelihood that patients will seek care and how they will respond to treatment.<span><sup>1, 5, 6</sup></span></p><p>Musculoskeletal research, similar to research in other areas of healthcare, does not always disaggregate results based on a patient's sex or gender.<span><sup>7</sup></span> Although some orthopedic surgery journals have explicit editorial standards on the topic of sex and gender in scientific reporting, and although international entities have published sensible guidelines about it,<span><sup>8</sup></span> we have observed that these standards are inconsistently applied.<span><sup>7</sup></span></p><p>Inattention to high-quality standards of scientific reporting can harm patients.<span><sup>9, 10</sup></span> Women have been underrepresented in medical research,<span><sup>11</sup></span> and this trend continues to varying degrees even today, despite mandates to remedy this disparity, at least in federally funded research.<span><sup>12, 13</sup></span> However, these mandates include no guidance about how data should be analyzed or reported, thereby limiting the impact of including more women in clinical studies. The care of women has been substantially compromised as a result<span><sup>14-18</sup></span>; not getting this right has sometimes harmed men with certain diagnoses as well.<span><sup>19</sup></span> As such, it is no stretch to say that doing better research—and improving how that research is reported in journals—would benefit our patients regardless of their sex or gender.</p><p>With this background in mind, leaders of the editorial boards of six orthopedic journals, along with leaders of funding agencies, as well as National Institutes of Health officials, met in November 2023 to discuss these issues. Following that meeting, those editors reached out to the Editors-in-Chief of all indexed orthopedic surgery journals, seeking concurrence on a few key themes pertaining to the reporting of sex and gender in musculoskeletal research.</p><p>We hope that by sharing these resolutions with readers, many of whom are also researchers and representatives on institutional review boards, institutional animal care and use committees, and/or funding agencies and organizations, the orthopedic research of the future will be both better designed and better reported.</p><p>Funding for this conference was made possible (in part) by (1R13AR082710–01) from the National Institute of Arthritis and Musculoskeleta","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1334","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140844786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Automatic Lenke classification of adolescent idiopathic scoliosis with deep learning","authors":"Baolin Zhang, Kanghao Chen, Haodong Yuan, Zhiheng Liao, Taifeng Zhou, Weiming Guo, Shen Zhao, Ruixuan Wang, Peiqiang Su","doi":"10.1002/jsp2.1327","DOIUrl":"https://doi.org/10.1002/jsp2.1327","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>The Lenke classification system is widely utilized as the preoperative evaluation protocol for adolescent idiopathic scoliosis (AIS). However, manual measurement is susceptible to observer-induced variability, which consequently impacts the evaluation of progression. The goal of this investigation was to develop an automated Lenke classification system utilizing innovative deep learning algorithms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the database from the First Affiliated Hospital of Sun Yat-sen University, the whole spinal x-rays images were retrospectively collected. Specifically, images collection was divided into AIS and control group. The control group consisted of individuals who underwent routine health checks and did not have scoliosis. Afterwards, relative features of all images were annotated. Deep learning was implemented through the utilization of the key-point based detection method to realize the vertebral detection, and Cobb angle measurement and scoliosis classification were performed based on relevant standards. Besides, the segmentation method was employed to achieve the recognition of lumbar vertebral pedicle to determine the type of lumbar spine modifier. Finally, the model performance was further quantitatively analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the study, a total of 2082 spinal x-ray images were collected from 407 AIS patients and 227 individuals in the control group. The model for vertebral detection achieved an F1-score of 0.809 for curve type evaluation and an F1-score of 0.901 for thoracic sagittal profile. The intraclass correlation efficient (ICC) of the Cobb angle measurement was 0.925. In the analysis of performance for vertebra pedicle segmentation model, the F1-score of lumbar modification profile was 0.942, the intersection over union (IOU) of the target pixels was 0.827, and the Hausdorff distance (HD) was 6.565 ± 2.583 mm. Specifically, the F1-score for ultimate Lenke type classifier was 0.885.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study has constructed an automated Lenke classification system by employing the deep learning networks to achieve the recognition pattern and feature extraction. Our models require further validation in additional cases in the future.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1327","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140814269","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}
JOR SpinePub Date : 2024-04-25DOI: 10.1002/jsp2.1322
Harrah R. Newman, Axel C. Moore, Kyle D. Meadows, Rachel L. Hilliard, Madeline S. Boyes, Edward J. Vresilovic, Thomas P. Schaer, Dawn M. Elliott
{"title":"Can axial loading restore in vivo disc geometry, opening pressure, and T2 relaxation time?","authors":"Harrah R. Newman, Axel C. Moore, Kyle D. Meadows, Rachel L. Hilliard, Madeline S. Boyes, Edward J. Vresilovic, Thomas P. Schaer, Dawn M. Elliott","doi":"10.1002/jsp2.1322","DOIUrl":"https://doi.org/10.1002/jsp2.1322","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cadaveric intervertebral discs are often studied for a variety of research questions, and outcomes are interpreted in the in vivo context. Unfortunately, the cadaveric disc does not inherently represent the LIVE condition, such that the disc structure (geometry), composition (T2 relaxation time), and mechanical function (opening pressure, OP) measured in the cadaver do not necessarily represent the in vivo disc.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted serial evaluations in the Yucatan minipig of disc geometry, T2 relaxation time, and OP to quantify the changes that occur with progressive dissection and used axial loading to restore the in vivo condition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found no difference in any parameter from LIVE to TORSO; thus, within 2 h of sacrifice, the TORSO disc can represent the LIVE condition. With serial dissection and sample preparation the disc height increased (SEGMENT height 18% higher than TORSO), OP decreased (POTTED was 67% lower than TORSO), and T2 time was unchanged. With axial loading, an imposed stress of 0.20–0.33 MPa returned the disc to in vivo, LIVE disc geometry and OP, although T2 time was decreased. There was a linear correlation between applied stress and OP, and this was conserved across multiple studies and species.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>To restore the LIVE disc state in human studies or other animal models, we recommend measuring the OP/stress relationship and using this relationship to select the applied stress necessary to recover the in vivo condition.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1322","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140648159","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}
JOR SpinePub Date : 2024-04-23DOI: 10.1002/jsp2.1332
Tamanna Rahman, Matthew J. Kibble, Gianluca Harbert, Nigel Smith, Erik Brewer, Thomas P. Schaer, Nicolas Newell
{"title":"Comparison of four in vitro test methods to assess nucleus pulposus replacement device expulsion risk","authors":"Tamanna Rahman, Matthew J. Kibble, Gianluca Harbert, Nigel Smith, Erik Brewer, Thomas P. Schaer, Nicolas Newell","doi":"10.1002/jsp2.1332","DOIUrl":"https://doi.org/10.1002/jsp2.1332","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nucleus replacement devices (NRDs) are not routinely used in clinic, predominantly due to the risk of device expulsion. Rigorous in vitro testing may enable failure mechanisms to be identified prior to clinical trials; however, current testing standards do not specify a particular expulsion test. Multiple methods have therefore been developed, complicating comparisons between NRD designs. Thus, this study assessed the effectiveness of four previously reported expulsion testing protocols; hula-hoop (Protocol 1), adapted hula-hoop (Protocol 2), eccentric cycling (Protocol 3), and ramp to failure (Protocol 4), applied to two NRDs, one preformed and one in situ curing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Nucleus material was removed from 40 bovine tail intervertebral disks. A NRD was inserted posteriorly into each cavity and the disks were subjected to one of four expulsion protocols.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NRD response was dependent on both the NRD design and the loading protocol. Protocol 1 resulted in higher migration and earlier failure rates compared to Protocol 2 in both NRDs. The preformed NRD was more likely to migrate when protocols incorporated rotation. The NRDs had equal migration (60%) and expulsion (60%) rates when using unilateral bending and ramp testing. Combining the results of multiple tests revealed complimentary information regarding the NRD response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Adapted hula-hoop (Protocol 2) and ramp to failure (Protocol 4), combined with fluoroscopic analysis, revealed complimentary insights regarding migration and failure risk. Therefore, when adopting the surgical approach and animal model used in this study, it is recommended that NRD performance be assessed using both a cyclic and ramp loading protocol.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1332","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639615","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}
JOR SpinePub Date : 2024-04-23DOI: 10.1002/jsp2.1333
Mary K. Heimann, Kelly Thompson, Gilian Gunsch, Shirley N. Tang, Brett Klamer, Kara Corps, Benjamin A. Walter, Sarah A. Moore, Devina Purmessur
{"title":"Characterization and modulation of the pro-inflammatory effects of immune cells in the canine intervertebral disk","authors":"Mary K. Heimann, Kelly Thompson, Gilian Gunsch, Shirley N. Tang, Brett Klamer, Kara Corps, Benjamin A. Walter, Sarah A. Moore, Devina Purmessur","doi":"10.1002/jsp2.1333","DOIUrl":"https://doi.org/10.1002/jsp2.1333","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disk (IVD) degeneration affects both humans and canines and is a major cause of low back pain (LBP). Mast cell (MC) and macrophage (MØ) infiltration has been identified in the pathogenesis of IVD degeneration (IVDD) in the human and rodent model but remains understudied in the canine. MC degranulation in the IVD leads to a pro-inflammatory cascade and activates protease activated receptor 2 (PAR2) on IVD cells. The objectives of the present study are to: (1) highlight the pathophysiological changes observed in the degenerate canine IVD, (2) further characterize the inflammatory effect of MCs co-cultured with canine nucleus pulposus (NP) cells, (3) evaluate the effect of construct stiffness on NP and MCs, and (4) identify potential therapeutics to mitigate pathologic changes in the IVD microenvironment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Canine IVD tissue was isolated from healthy autopsy research dogs (beagle) and pet dogs undergoing laminectomy for IVD herniation. Morphology, protein content, and inflammatory markers were assessed. NP cells isolated from healthy autopsy (Mongrel hounds) tissue were co-cultured with canine MCs within agarose constructs and treated with cromolyn sodium (CS) and PAR2 antagonist (PAR2A). Gene expression, sulfated glycosaminoglycan content, and stiffness of constructs were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CD 31+ blood vessels, mast cell tryptase, and macrophage CD 163+ were increased in the degenerate surgical canine tissue compared to healthy autopsy. Pro-inflammatory genes were upregulated when canine NP cells were co-cultured with MCs and the stiffer microenvironment enhanced these effects. Treatment with CS and PAR2 inhibitors mediated key pro-inflammatory markers in canine NP cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>There is increased MC, MØs, and vascular ingrowth in the degenerate canine IVD tissue, similar to observations in the clinical population with IVDD and LBP. MCs co-cultured with canine NP cells drive inflammation, and CS and PAR2A are potential therapeutics that may mitigate the pathophysiology of IVDD in vitro.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1333","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639616","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}
JOR SpinePub Date : 2024-04-17DOI: 10.1002/jsp2.1325
Tao Xu, Hongqi Zhao, Jian Li, Xuan Fang, Hua Wu, Weihua Hu
{"title":"Apigetrin alleviates intervertebral disk degeneration by regulating nucleus pulposus cell autophagy","authors":"Tao Xu, Hongqi Zhao, Jian Li, Xuan Fang, Hua Wu, Weihua Hu","doi":"10.1002/jsp2.1325","DOIUrl":"https://doi.org/10.1002/jsp2.1325","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disk degeneration (IVDD) is a common spine disease, and inflammation is considered to be one of its main pathogenesis. Apigetrin (API) is a natural bioactive flavonoid isolated from various herbal medicines and shows attractive anti-inflammatory and antioxidative properties; whereas, there is no exploration of the therapeutic potential of API on IVDD. Here, we aim to explore the potential role of API on IVDD in vivo and in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In vitro, western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence analysis were implemented to explore the bioactivity of API on interleukin-1 beta (IL-1β)-induced inflammatory changes in nucleus pulposus cells (NPCs). In vivo, histological staining and immunohistochemistry were employed to investigate the histological changes of intervertebral disk sections on puncture-induced IVDD rat models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In vitro, API played a crucial role in anti-inflammation and autophagy enhancement in IL-1β-induced NPCs. API improved inflammation by inhibiting the nuclear factor-kappaB and mitogen-activated protein kinas pathways, whereas it promoted autophagy via the phosphatidylinositol 3-kinase/AKT/mammalian target of the rapamycin pathway. Furthermore, in vivo experiment illustrated that API mitigates the IVDD progression in puncture-induced IVDD model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>API inhibited degenerative phenotypes and promoted autophagy in vivo and in vitro IVDD models. Those suggested that API might be a potential drug or target for IVDD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1325","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140559650","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}
JOR SpinePub Date : 2024-04-17DOI: 10.1002/jsp2.1326
Frank Niemeyer, Fabio Galbusera, Martijn Beukers, René Jonas, Youping Tao, Marion Fusellier, Marianna A. Tryfonidou, Cornelia Neidlinger-Wilke, Annette Kienle, Hans-Joachim Wilke
{"title":"Automatic grading of intervertebral disc degeneration in lumbar dog spines","authors":"Frank Niemeyer, Fabio Galbusera, Martijn Beukers, René Jonas, Youping Tao, Marion Fusellier, Marianna A. Tryfonidou, Cornelia Neidlinger-Wilke, Annette Kienle, Hans-Joachim Wilke","doi":"10.1002/jsp2.1326","DOIUrl":"https://doi.org/10.1002/jsp2.1326","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration is frequent in dogs and can be associated with symptoms and functional impairments. The degree of disc degeneration can be assessed on T2-weighted MRI scans using the Pfirrmann classification scheme, which was developed for the human spine. However, it could also be used to quantify the effectiveness of disc regeneration therapies. We developed and tested a deep learning tool able to automatically score the degree of disc degeneration in dog spines, starting from an existing model designed to process images of human patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MRI midsagittal scans of 5991 lumbar discs of dog patients were collected and manually evaluated with the Pfirrmann scheme and a modified scheme with transitional grades. A deep learning model was trained to classify the disc images based on the two schemes and tested by comparing its performance with the model processing human images.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The determination of the Pfirrmann grade showed sensitivities higher than 83% for all degeneration grades, except for grade 5, which is rare in dog spines, and high specificities. In comparison, the correspondent human model had slightly higher sensitivities, on average 90% versus 85% for the canine model. The modified scheme with the fractional grades did not show significant advantages with respect to the original Pfirrmann grades.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The novel tool was able to accurately and reliably score the severity of disc degeneration in dogs, although with a performance inferior than that of the human model. The tool has potential in the clinical management of disc degeneration in canine patients as well as in longitudinal studies evaluating regenerative therapies in dogs used as animal models of human disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 2","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1326","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140559649","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}