JOR Spine最新文献

{"title":"Human Placental Extract as a Promising Epidural Therapy for Lumbar Spinal Stenosis: Enhancing Axonal Plasticity and Mitigating Pain and Inflammation in a Rat Model","authors":"Jin Young Hong,&nbsp;Hyun Kim,&nbsp;Wan-Jin Jeon,&nbsp;Changhwan Yeo,&nbsp;Junseon Lee,&nbsp;Hyunseong Kim,&nbsp;Yoon Jae Lee,&nbsp;In-Hyuk Ha","doi":"10.1002/jsp2.70085","DOIUrl":"https://doi.org/10.1002/jsp2.70085","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Epidural injections treat lumbar spinal stenosis (LSS) by targeting localized inflammation and tissue damage. However, current medications such as corticosteroids and local anesthetics often have limited efficacy and significant adverse effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Human placental extract (HPE), with regenerative and anti-inflammatory properties, was tested for its axon-promoting and pain-relieving effects in an in vitro model using dorsal root ganglion neurons exposed to hydrogen peroxide (H₂O₂).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Various HPE doses were applied, and 2.5 or 5 mg/mL enhanced cell viability and neurite outgrowth while alleviating the increased expression of pain-related markers (IB4, CGRP, TRPV1) caused by H₂O₂ in a dose-dependent manner. Subsequently, rats with LSS received epidural injections of 10 or 20 mg/kg HPE five times weekly for four weeks. In vivo results showed that repeated HPE injections significantly reduced ED1⁺ macrophages and altered the expression of M1 (iNOS, TNF-α, COX-2) and M2 (Arg1, CD206) macrophage markers. Pain-related markers (TRPV1, IB4, CGRP, NF200) and genes (<i>Il1rn</i>, <i>Scn9a</i>) were significantly downregulated in 3D dorsal root ganglion tissues. Additionally, the 3D spinal cord exhibited increased serotonergic axons and upregulated expression of genes related to axonal growth and neurotrophic factors (<i>Nefh, Ngf, Bdnf, Gap43</i>).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings suggest that repeated epidural injections of human placental extract in LSS rats can improve locomotor function. This underscores the potential benefits of human placental extract as an epidural agent, enhancing the recovery process and offering a new and minimally invasive treatment strategy for LSS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309145","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":"Complex In Vivo Motion of the Bovine Tail Provides Unique Insights Into Intervertebral Disc Adaptation","authors":"Arthur J. Michalek,&nbsp;Isabelle M. Wood,&nbsp;Daniela Gonzalez Carranza,&nbsp;Lindsay Ferlito","doi":"10.1002/jsp2.70084","DOIUrl":"https://doi.org/10.1002/jsp2.70084","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The intervertebral disc (IVD) of the bovine tail is a commonly used research analogue for the human disc at the organ, tissue, and cellular levels. While these tails are subjected to thousands of dynamic motion events daily, little is known about how these motions might induce tissue remodeling, particularly in the outer annulus fibrosus (AF) of IVDs connecting adjacent vertebrae. This study hypothesized that despite the similarities in geometry and biochemical composition of IVDs in the bovine tail, level-wise variations in repetitive in-vivo motion would be associated with tissue level adaptations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In-vivo active range of motion (RoM) was measured by placing inertial measurement unit sensors on the tails of adult cows and using a multi-segment rigid body model to calculate level-wise flexion-extension and lateral bending angles. Level-wise passive RoM was measured from cadaveric adult bovine tails in flexion, extension, and lateral bending with skin and muscles removed. IVDs were extracted for measurement of height, diameters, AF radial thicknesses, and AF fiber crimp periods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In-vivo joint RoM was found to vary drastically by level, largely due to a prominent second order mode with inflection point at the fourth joint. Joint levels near this inflection point were found to have the highest passive RoMs. In the proximal tail, decreased RoM was associated with an increased fiber crimp period in the outer AF, while in the distal tail it was associated with increased AF thickness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Taken together, these findings suggest that IVDs in the bovine tail respond to repeated complex dynamic motions through a process of adaptation at the mesoscale (AF thickening during growth) and microscale (residual strain accumulation in the mature state). The bovine tail thus provides a powerful tool for modeling how the human lumbar intervertebral disc may remodel in response to changes in exposure to repetitive motions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309146","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":"Injection Volume Is a Better Predictor of Stiffness Restoration Than Injection Force in an In Vitro Study of Nucleus Augmentation of the Intervertebral Disc","authors":"J. P. Warren,&nbsp;A. R. Dixon,&nbsp;M. P. Culbert,&nbsp;A. Khan,&nbsp;M. Mengoni,&nbsp;R. K. Wilcox","doi":"10.1002/jsp2.70081","DOIUrl":"https://doi.org/10.1002/jsp2.70081","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Nucleus augmentation has been proposed as an early-stage intervention for intervertebral disc degeneration and involves the injection of a biomaterial into the nucleus to restore disc height and functionality. The aim of this work was to identify clinically relevant quantitative measures that indicate the mechanical performance of the disc following nucleus augmentation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Bovine tail bone-disc-bone units (<i>n</i> = 22) were mechanically tested under cyclic loading sequentially in native, artificially degenerated, and treated states. Treatment involved injection of a peptide-glycosaminoglycan mixture into the degenerated disc to a predetermined load using a syringe driver with an integrated force sensor. The stiffness restoration of the treatment was determined by comparing the biomechanical behavior of the native state to the treated state of each disc. The stiffness restoration was then compared against clinically quantifiable parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No significant biomechanical differences were observed between the native and treated states, but both were significantly different from the degenerated state. The force delivered during injection was found to ramp to a steady state, followed by a final rapid increase; however, all measures associated with injection force poorly correlated with the level of stiffness restoration. Volume injected and change in disc height from injection had the strongest relationship to stiffness restoration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This work showed that measuring the injection force for injectable treatments of the disc can provide lower and upper limits for delivery, but direct measures are stronger indicators of disc stiffness restoration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244647","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":"The Role of Adipokines in Spinal Disease: A Narrative Review","authors":"Jake M. McDonnell,&nbsp;Stacey Darwish,&nbsp;Joseph S. Butler,&nbsp;Conor T. Buckley","doi":"10.1002/jsp2.70083","DOIUrl":"https://doi.org/10.1002/jsp2.70083","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Adipokines are bioactive molecules secreted by adipose tissue that influence both local and systemic physiological processes. Although adipokine dysregulation has been widely implicated in the pathogenesis of cardiovascular, gastrointestinal, nervous, immune, and musculoskeletal disorders- especially osteoarthritis, rheumatoid arthritis, and osteoporosis- their involvement in spinal pathology remains comparatively underinvestigated. Recent evidence indicates that certain adipokines may influence spinal disease progression by affecting bone, intervertebral discs, musculature, and neural structures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive literature review was conducted to evaluate preclinical and clinical studies investigating the role of adipokines in spinal pathology. PubMed and related databases were searched for studies reporting associations between adipokine expression and structural or functional changes in spinal tissues, including vertebral bone, intervertebral discs, paraspinal muscles, spinal ligaments, and the spinal cord. Particular attention was given to mechanistic insights and translational relevance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The review identified emerging evidence implicating several adipokines, including leptin, adiponectin, resistin, and visfatin, in degenerative and inflammatory changes across various spinal structures. Adipokines were found to influence matrix degradation, bone turnover, muscle atrophy, and neural inflammation through cytokine signaling, oxidative stress, and metabolic dysregulation. However, findings are often heterogeneous and context-dependent, with limited longitudinal or interventional data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Adipokines represent a promising yet underexplored avenue in spinal disease research. Their diverse functions in both structural and metabolic regulation highlight their potential as both biomarkers and therapeutic targets. Further mechanistic and clinical studies are needed to elucidate causal relationships and therapeutic efficacy, particularly in degenerative spine disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144206379","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":"Intradiscal Mesenchymal Stromal Cell Therapy for the Treatment of Low Back Pain Due to Moderate-to-Advanced Multilevel Disc Degeneration: A Preliminary Report of a Double-Blind, Phase IIB Randomized Clinical Trial (DREAM Study)","authors":"Gianluca Vadalà,&nbsp;Fabrizio Russo,&nbsp;Cristiana Lavazza,&nbsp;Giorgia Petrucci,&nbsp;Luca Ambrosio,&nbsp;Silvia Budelli,&nbsp;Elisa Montelatici,&nbsp;Giuseppina Di Giacomo,&nbsp;Claudia Cicione,&nbsp;Veronica Tilotta,&nbsp;Giuseppe Francesco Papalia,&nbsp;Matteo Pileri,&nbsp;Amalia Bruno,&nbsp;Salvatore La Rosa,&nbsp;Emilio Carrino,&nbsp;Eliodoro Faiella,&nbsp;Massimiliano Carassiti,&nbsp;Lorenza Lazzari,&nbsp;Rocco Papalia,&nbsp;Vincenzo Denaro","doi":"10.1002/jsp2.70086","DOIUrl":"https://doi.org/10.1002/jsp2.70086","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Low back pain (LBP) is a leading cause of disability worldwide, often associated with intervertebral disc degeneration (IDD). Mesenchymal stromal cells (MSCs) have emerged as a promising regenerative therapy for IDD due to their ability to promote tissue repair. This phase IIB randomized controlled trial aimed to evaluate the safety and efficacy of autologous bone marrow-derived MSC (BM-MSC) intradiscal injections in patients with chronic LBP due to moderate-to-advanced multilevel IDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fifty-two patients with chronic LBP unresponsive to conservative treatments with moderate-to-advanced IDD at up to three lumbar levels were included. Participants were randomized to receive either BM-MSCs or a sham procedure. Clinical outcomes, including pain intensity (VAS), disability (ODI), and quality of life (SF-36), were assessed at baseline, 1-, 3-, and 6-months postinjection. Structural changes were evaluated via MRI using Pfirrmann grading, disc height index (DHI), and T2 mapping at baseline, 3 and 6 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 52 enrolled patients, 46 completed the 6-month follow-up (BM-MSC group: <i>n</i> = 21; sham group: <i>n</i> = 25). BM-MSC injections were well-tolerated, with no major adverse events reported. Structural improvements were observed in the BM-MSC group, including significant increases in DHI and nonsignificant improvements in T2 relaxation times at 3 and 6 months. Modified Pfirrmann grades showed transient improvement at 3 months but returned to baseline at 6 months. Despite these radiological changes, clinical outcomes such as VAS, ODI, and SF-36 scores improved similarly in both groups without significant intergroup differences at any timepoint. The sham group demonstrated slightly greater improvements in disability (ODI) and physical quality-of-life scores (SF-36 PCS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Autologous BM-MSC intradiscal injection is a safe and promising approach in patients with chronic LBP due to moderate-to-advanced multilevel IDD. However, despite these regenerative effects, no significant clinical advantages over the sham procedure were observed within 6 months of follow-up.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197411","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":"Causal Relationship Between Gut Microbiota, Blood Metabolites, and Intervertebral Disc Degeneration: A Two-Step, Two-Sample Bidirectional Mendelian Randomization Study","authors":"Yi-Ping Zheng,&nbsp;Dong-Lin Yang,&nbsp;Lu-Yang Wang,&nbsp;Xi-Zhong Zhu,&nbsp;Xing-Chen Li,&nbsp;Jin-Hong Miao,&nbsp;Yu-Sheng Xu","doi":"10.1002/jsp2.70078","DOIUrl":"https://doi.org/10.1002/jsp2.70078","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Some studies have shown that gut microbiota may be associated with intervertebral disc degeneration. However, the causal effects between gut microbiota and IVDD and whether blood metabolites act as a mediator remain unclear. The objective of this study was to investigate the causal relationship between gut microbiota and intervertebral disc herniation, with a focus on the potential mediating role of blood metabolites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Gut microbiota, blood metabolites, and IVDD data were identified from large-scale genome-wide association studies (GWAS) summary data. Then we used Mendelian randomization analysis to investigate the causal relationships between gut microbiota, blood metabolites, and intervertebral disc degeneration, using the inverse variance-weighted method as the primary outcome measure. Subsequently, we conducted sensitivity analyses to ascertain the robustness of the results by testing for heterogeneity and horizontal pleiotropy. In addition, we explored blood metabolites as a mediating factor in the pathway from gut microbiota to IVDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 6 taxa that were strongly associated with the incidence of intervertebral disc herniation. There were 8 positive and 13 negative causal effects between genetic liability in the blood metabolites and IVDD. The mediation analysis revealed that the connections among genus Comamonas B, family Halomonadaceae, family UBA6960, and IVDD were mediated by ADP to glycine ratio, 1,3-dimethylurate levels, 3-hydroxy-2-methylpyridine sulfate levels, and Histidine levels. Each of these accounted for 7.77%, 9.04%, 12.56%, and 11.76%, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study provides evidence supporting a potential causal relationship between certain microbial taxa and intervertebral disc degeneration. This study focuses on the mediation of specific blood metabolites, which suggests that they may represent potential targets for intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171770","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":"Crosstalk Between Ferroptosis and Cuproptosis in Intervertebral Disc Degeneration: Mechanisms, Therapeutic Targets, and Future Directions","authors":"Zhongpan Li,&nbsp;Liangwei Wang,&nbsp;Xiaojun Wu,&nbsp;Rui Huang,&nbsp;Yi Yuan","doi":"10.1002/jsp2.70080","DOIUrl":"https://doi.org/10.1002/jsp2.70080","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IVDD) is a prevalent degenerative disease, with low back pain as its primary clinical symptom, imposing significant burdens on individuals and society. With the aging population, IVDD is becoming an inevitable challenge. Current research indicates that the pathogenesis of IVDD is primarily driven by aging, mechanical stress, cell death, and genetics, leading to the loss of nucleus pulposus and degradation of the extracellular matrix within the intervertebral disc.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This review aims to explore the relationship between the mechanisms of ferroptosis and cuproptosis, two newly discovered modes of cell death, and their potential as therapeutic targets for IVDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a comprehensive review of recent studies on ferroptosis and cuproptosis in IVDD, analyzing the mechanisms of these cell death patterns and their potential role in IVDD progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ferroptosis and cuproptosis have been found to be closely related to IVDD. These cell death modes are implicated in the pathological processes of IVDD, suggesting a potential link between their mechanisms and the disease's progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The mechanisms of ferroptosis and cuproptosis are closely related to IVDD, and these pathways may be potential targets for IVDD treatment, providing new directions for clinical treatment of IVDD and future research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171801","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":"In Vivo Measurements Reveal Increased Nucleus Pulposus Lactate and Oxygen Concentrations in a Goat Model of Intervertebral Disc Degeneration","authors":"Karthikeyan Rajagopal,&nbsp;Thomas P. Schaer,&nbsp;Kyle D. Meadows,&nbsp;Madeline Boyes,&nbsp;Rachel Hilliard,&nbsp;John C. O'Donnell,&nbsp;George R. Dodge,&nbsp;Dmitriy Petrov,&nbsp;Dawn M. Elliott,&nbsp;Robert L. Mauck,&nbsp;Lachlan J. Smith,&nbsp;Neil R. Malhotra","doi":"10.1002/jsp2.70076","DOIUrl":"https://doi.org/10.1002/jsp2.70076","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Intervertebral disc degeneration is strongly implicated as a cause of low back pain. Although the precise pathophysiological mechanisms remain elusive, perturbations in nutrition that adversely impact the cellular microenvironment of the central nucleus pulposus (NP) may be contributing factors. A comprehensive understanding of this microenvironment, including changes in nutrient availability as a function of degeneration, is critical for the development of effective cell-based treatments. The goal of this study was to adapt brain tissue oxygen probes and microdialysis catheters for in situ determination of relative NP oxygen, glucose, and lactate levels in a preclinical goat model of disc degeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Following ex vivo technical refinement in bovine caudal discs, baseline metabolite measurements were performed in vivo in the lumbar discs of 3 large frame goats. Degeneration was then induced via injection of chondroitinase ABC (ChABC) into the NP, and measurements were repeated after 12 weeks. Degeneration severity was graded using magnetic resonance imaging (MRI) and histology, and vertebral endplate porosity was assessed using microcomputed tomography.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Oxygen and lactate levels in goat NPs were significantly higher in degenerate compared to healthy discs, while glucose levels were not significantly different. ChABC-injected discs exhibited higher vertebral endplate porosity, worse histological and MRI grades, and a spectrum of cartilage endplate damage compared to healthy discs. There were significant positive correlations between MRI grade and both NP oxygen and lactate levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>We successfully adapted techniques including surgical placement, equilibration time, flow rate, and detection method for in situ measurement of oxygen, glucose, and lactate in a goat model of disc degeneration. Interestingly, while increased lactate with degeneration was expected, increased oxygen levels were unexpected. Our findings may, in part, be explained by associated alterations in disc and endplate structure, and motivate future studies to comprehensively establish the underlying mechanisms in this model.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148286","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":"In Vitro Validation of Pulsed Electromagnetic Field (PEMF) as an Effective Countermeasure Against Inflammatory-Mediated Intervertebral Disc Degeneration","authors":"Laura Guarnaccia,&nbsp;Laura Begani,&nbsp;Silvana Pileggi,&nbsp;Mauro Pluderi,&nbsp;Stefano Borsa,&nbsp;Claudia Fanizzi,&nbsp;Massimiliano Domenico Rizzaro,&nbsp;Giorgio Fiore,&nbsp;Laura Fontana,&nbsp;Rolando Campanella,&nbsp;Chiara Cordiglieri,&nbsp;Chiara Gaudino,&nbsp;Giovanni A. Alotta,&nbsp;Monica Miozzo,&nbsp;Emanuele Garzia,&nbsp;Emanuela Barilla,&nbsp;Lorenzo Fassina,&nbsp;Laura Riboni,&nbsp;Marco Locatelli,&nbsp;Giovanni Marfia,&nbsp;Stefania E. Navone","doi":"10.1002/jsp2.70077","DOIUrl":"https://doi.org/10.1002/jsp2.70077","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc (IVD) degeneration (IDD) is the main contributor to chronic low back pain (LBP), the leading cause of disability worldwide, with a significant impact on the quality of life and health of common people. The etiology of IDD is still unclear, but it has been largely demonstrated the crucial role of inflammation and neuroinflammation in the pathological and degenerative cascade of events characterizing IVD degeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>In this study, we evaluated the potential therapeutic effect of pulsed electromagnetic field (PEMF) on human degenerated IVD (D-IVD) cells collected from patients who underwent discectomy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials &amp; Methods</h3>\u0000 \u0000 <p>The experimental plan to test our hypothesis, involved viability assay, reactive oxide species/nitrite production, gene, and protein expression. To recapitulate the pro-inflammatory disc microenvironment occurring during IDD, interleukin-1β (IL-1β) was administered to IVD cell culture. Then, to dissect the contribution of neuroinflammatory condition to immune component, microglial cells were co-cultured with IVD-conditioned media, and viability and expression of inflammatory markers were detected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our data prove that in the IVD degenerative microenvironment, the increase of pro-inflammatory mediators, extracellular matrix degradative enzymes, and neuroinflammatory markers could be reduced by PEMF therapy, resulting in an overall improvement of degenerative condition and LBP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results represent an impactful novelty for the management of people suffering from LPB, in terms of symptom relief and reduction of social-health system burden.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085460","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":"TNFα Receptor 1 and Not Receptor 2 Affect Annulus Fibrosus and Nucleus Pulposus Response to Cytokine Challenge in a Rat Model","authors":"Timothy D. Jacobsen,&nbsp;S. Olga Yiantsos,&nbsp;Jennifer Gansau,&nbsp;James Meyers,&nbsp;Damien Laudier,&nbsp;James C. Iatridis","doi":"10.1002/jsp2.70070","DOIUrl":"https://doi.org/10.1002/jsp2.70070","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Painful intervertebral disc (IVD) degeneration (IVDD) involves chronic inflammation. Developing translational immunomodulatory strategies for IVDD is a priority with tumor necrosis factor alpha (TNFα) signaling an important target. TNFα binds to 2 receptors (TNFRs), with TNFR1 signaling promoting catabolism and apoptosis and TNFR2 signaling promoting anabolism and proliferation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study developed translational strategies to evaluate and modulate TNFR1 and TNFR2 signaling in rat in vivo and in vitro IVDD models. We used blocking antibodies, the TNFR2-activator Atsttrin, and small molecule inhibitors of TNFR1 to discern distinct TNFR1 and TNFR2-effects on annulus fibrosus (AF) and nucleus pulposus (NP) cells and to identify effective strategies for modulating specific TNFRs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TNFR1 was significantly increased with IVDD in vivo in the NP while TNFR2 was unaffected with very faint staining. TNFR1-specific small molecule inhibitors were effective in reducing catabolic effects of TNFα, highlighting the efficacy of this small molecule strategy for TNFR1 signaling modulation. Meanwhile, TNFR1 and TNFR2 inhibition in vitro was not effective with blocking antibodies on NP or AF cells, likely due to species-specificity of available blocking antibodies. Further, TNFR2 activation with Atsttrin was similarly ineffective, likely due to extremely low TNFR2 levels in both AF and NP cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>TNFα receptor-specific signaling is important in rat IVDD in vivo and in vitro. TNFR1 inhibition was more effective with small molecules than using blocking antibodies. Low levels of TNFR2 in rat AF and NP cells and lack of efficacy of TNFR2-activator Atsttrin suggest native AF and NP cells have little capacity for TNFR2-dependent IVD repair.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085459","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}