JOR Spine最新文献

{"title":"Mechanism of Intervertebral Disc Degeneration via the β-Catenin/CCL2 Pathway in Sox9 Conditional Knockout Mice","authors":"Khaled Aboushaala,&nbsp;Ana Chee,&nbsp;Frank Ko,&nbsp;Jad Alkhudari,&nbsp;Saurav Sumughan,&nbsp;Howard S. An,&nbsp;Dino Samartzis,&nbsp;Chun-do Oh","doi":"10.1002/jsp2.70053","DOIUrl":"https://doi.org/10.1002/jsp2.70053","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Degenerative changes in the intervertebral disc (IVD) are known to be a main cause of low back pain (LBP), oftentimes necessitating interventions that may or may not be successful due to a lack of understanding in the degenerative phenotype and its mechanisms. Understanding the molecular mechanisms of disc degeneration can help design new therapies to induce disc regeneration and reduce back pain. This work aimed to understand the effects of conditional deletion of Sox9 in aggrecan-expressing cells on intervertebral disc degeneration and its underlying mechanisms in mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study utilized <i>Agc1-CreERT2;Sox9</i>^{<i>flox/flox</i>} mice to investigate the effects of SOX9 deletion on IVD degeneration and associated pain behaviors. Mice were administered tamoxifen to induce conditional gene deletion of Sox9. Structural and degenerative phenotypes of the spine were assessed by a histological scoring system and micro-computed tomography (microCT). Pain behaviors were evaluated through mechanical allodynia testing and the LABORAS system for spontaneous behavior assessment. Immunohistochemistry identified the expression of proteins of interest, which were further examined by Western blotting. Lastly, quantitative real-time PCR and promoter assays on IVD cells were used to examine inflammatory and signaling pathways induced by Sox9 deletion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Crossing <i>Agc1-CreERT2</i> mice with <i>Sox9</i>^{<i>flox/flox</i>} mice revealed that <i>Sox9</i> conditional deletion (<i>Sox9</i>^<i>cKO</i>) in cartilage tissues causes IVD degeneration and pain behavior. <i>Sox9</i>^<i>cKO</i> mice spines had narrowed intervertebral disc spaces and disorganized IVD tissues. <i>Sox9</i> deletion also increased β-catenin, C-C motif chemokine ligand 2 (CCL2), and Glial cell line-derived neurotrophic factor (GDNF) expression in the IVD, suggesting their roles in disc pain and degeneration and the importance of the β-catenin/CCL2 pathway in these processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Deletion of <i>Sox9</i> in Aggrecan-expressing IVD tissues affects disc degeneration and associated pain behaviors through the β–catenin–CCL2 pathway. Such findings can lead to more targeted, personalized therapeutics in the future to address discogenic origins of LBP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497306","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":"Gene Expression Changes Precede Elevated Mechanical Sensitivity in the Mouse Intervertebral Disc Injury Model","authors":"Zuozhen Tian,&nbsp;Ken Chen,&nbsp;Frances S. Shofer,&nbsp;Brianna Ciesielski,&nbsp;Huan Wang,&nbsp;W. Timothy O'Brien,&nbsp;Ling Qin,&nbsp;Yejia Zhang","doi":"10.1002/jsp2.70049","DOIUrl":"https://doi.org/10.1002/jsp2.70049","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Back pain after intervertebral disc (IVD) injury is a common clinical problem. Previous work examining early molecular changes post injury mainly used a candidate marker approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, gene expression in the injured and intact mouse tail IVDs was determined with a nonbiased whole transcriptome approach and related to subsequent pain behavior. Mouse tail IVD injury was induced by a needle puncture. Whole murine transcriptome was determined by RNASeq. Transcriptomes of injured IVDs were compared with those of intact controls by bioinformatic methods. Mechanical allodynia was assessed by the Von Frey method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 17,722 murine genes with meaningful expressions, 7242 genes were differentially expressed (<i>P.adj</i> ⟨ 0.01). Ontology study of upregulated genes revealed that leukocyte migration was the most enriched biological process, and network analysis showed that Tnfa had the most protein–protein interactions. The most enriched downregulated pathways were related to the pattern specification process. Mechanical allodynia persisted at the 4-week end point.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The RNASeq data revealed numerous early genes that participate in inflammation and repair processes post IVD injury. Mechanical allodynia followed these gene expression changes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475409","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":"Parallel Networks to Predict TIMP and Protease Cell Activity of Nucleus Pulposus Cells Exposed and Not Exposed to Pro-Inflammatory Cytokines","authors":"L. Baumgartner,&nbsp;S. Witta,&nbsp;J. Noailly","doi":"10.1002/jsp2.70051","DOIUrl":"https://doi.org/10.1002/jsp2.70051","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc (IVD) degeneration is characterized by a disruption of the balance between anabolic and catabolic cellular processes. Within the nucleus pulposus (NP), this involves increased levels of the pro-inflammatory cytokines interleukin 1beta (IL1B) and tumor necrosis factor (TNF) and an upregulation of the protease families matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS). Primary inhibitors of these proteases are the tissue inhibitors of matrix metalloproteinases (TIMP). This work aims at contributing to a better understanding of the dynamics among proteases, TIMP, and pro-inflammatory cytokines within the complex, multifactorial environment of the NP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The Parallel Network (PN)-Methodology was used to estimate relative mRNA expressions of TIMP1–3, MMP3, and ADAMTS4 for five simulated human activities: walking, sitting, jogging, hiking with 20 kg extra weight, and exposure to high vibration. Simulations were executed for nutrient conditions in non- and early-degenerated IVD approximations. To estimate the impact of cytokines, the PN-Methodology inferred relative protein levels for IL1B and TNF, reintegrated as secondary stimuli into the network.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TIMP1 and TIMP2 expressions were found to be overall lower than TIMP3 expression. In the absence of pro-inflammatory cytokines, MMP3 and/or ADAMTS4 expressions were strongly downregulated in all conditions but vibration and hiking with extra weight. Pro-inflammatory cytokine exposure resulted in an impaired inhibition of MMP3, rather than of ADAMTS4, progressively rising with increasing nutrient deprivation. TNF mRNA was less expressed than IL1B. However, at the protein level, TNF was mainly responsible for the catabolic shift in the simulated pro-inflammatory environment. Overall, results agreed with previous experimental findings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The PN-Methodology successfully allowed the exploration of the relative dynamics of TIMP and protease regulations in different mechanical, nutritional, and inflammatory environments in the NP. It shall stand as a comprehensive tool to integrate in vitro model results in IVD research and approximate NP cell activities in complex multifactorial environments.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447211","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":"Do we know more about the mechanobiology of the intervertebral disc in space than on Earth?","authors":"Timothy Patrick Holsgrove,&nbsp;Isabelle Ebisch,&nbsp;Daniela Lazaro-Pacheco","doi":"10.1002/jsp2.70024","DOIUrl":"https://doi.org/10.1002/jsp2.70024","url":null,"abstract":"<p>This work provides a perspective on the loading protocols used in whole-organ interverterbal disc culture studies using bioreactors. We put this in the context of in vivo spinal loading, and we put forward the case that the majority of previous bioreactor studies have more in common with spinal loading in space than on Earth. Finally, we provide an outlook for the future of bioreactor research, to provide data more relevant to spinal loading on Earth, and maximize the translational potential of findings to the clinical setting.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431737","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":"Transient Receptor Potential Vanilloid 4 Knockdown Decreases Extracellular Matrix Synthesis via Autophagy Suppression in the Rat Intervertebral Disc","authors":"Tomoya Matsuo,&nbsp;Yoshiki Takeoka,&nbsp;Takashi Yurube,&nbsp;Takeru Tsujimoto,&nbsp;Yutaro Kanda,&nbsp;Kunihiko Miyazaki,&nbsp;Hiroki Ohnishi,&nbsp;Masao Ryu,&nbsp;Naotoshi Kumagai,&nbsp;Kohei Kuroshima,&nbsp;Yoshiaki Hiranaka,&nbsp;Ryosuke Kuroda,&nbsp;Kenichiro Kakutani","doi":"10.1002/jsp2.70046","DOIUrl":"https://doi.org/10.1002/jsp2.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Transient receptor potential vanilloid 4 (TRPV4) has been identified as a Ca²⁺-permeable channel and is activated under physiological mechanical stimulation in disc nucleus pulposus (NP) cells. Meanwhile, the Ca²⁺-dependent AMP-activated protein kinase (AMPK)/mTOR pathway activates autophagy in notochordal cells. We hypothesized that TRPV4 is involved in the maintenance of intradiscal homeostasis via autophagy. Our objective was to elucidate the role of TRPV4 in extracellular matrix (ECM) metabolism and autophagy in the rat intervertebral disc through a loss-of-function study with the RNA interference (RNAi) technique.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In vitro study: Small interfering RNA (siRNA) was applied to knockdown TRPV4 by the reverse transfection method in rat disc NP cells. Expression of TRPV4, AMPK/mTOR pathway-related markers, and autophagy markers were measured by Western blotting (WB). Next, ECM metabolism was assessed under serum starvation and/or proinflammatory interleukin-1 beta (IL-1β) stimulation. In vivo study: TRPV4 and control siRNAs were injected into rat discs. To confirm in vivo transfection, WB for TRPV4 was conducted in rat disc NP-tissue protein extracts 2, 28, and 56 days after injection. Furthermore, 24-h temporary static compression-induced disruption of TRPV4 siRNA-injected discs was observed by radiography, histomorphology, and immunofluorescence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In vitro study: In disc cells, three different TRPV4 siRNAs consistently suppressed autophagy with TRPV4 protein knockdown (mean 33.2% [95% CI: −50.8, −15.5], 44.1% [−61.7, −26.4], 58.3% [−76.0, −40.7]). ECM metabolism was significantly suppressed by TRPV4 RNAi under proinflammatory IL-1β stimulation. In vivo study: The WB displayed sustained decreases in TRPV4 protein expression 2, 28, and 56 days after injection. Under the loaded condition, TRPV4 siRNA-injected discs presented radiographic height loss ([−31.7, −7.75]), histomorphological damage ([0.300, 4.70]), and immunofluorescent suppression of autophagy ([1.61, 20.5]) and ECM metabolism ([−25.2, −6.41]) compared to control siRNA-injected discs at 56 days.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The TRPV4 could be a therapeutic target for intervertebral disc diseases via modulating autophagy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431573","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":"Ex Vivo and In Vitro Proteomic Approach to Elucidate the Relevance of IL-4 and IL-10 in Intervertebral Disc Pathophysiology","authors":"Paola Bermudez-Lekerika,&nbsp;Sofia Tseranidou,&nbsp;Exarchos Kanelis,&nbsp;Andrea Nüesch,&nbsp;Katherine B. Crump,&nbsp;Leonidas G. Alexopoulos,&nbsp;Karin Wuertz-Kozak,&nbsp;Jérôme Noailly,&nbsp;Christine L. Le Maitre,&nbsp;Benjamin Gantenbein","doi":"10.1002/jsp2.70048","DOIUrl":"https://doi.org/10.1002/jsp2.70048","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study investigates the native presence and potential anabolic effects of interleukin (IL)-4 and IL-10 in the human intervertebral disc (IVD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Human nucleus pulposus (NP) cells cultured in 3D from trauma and degenerate IVDs and NP explants were stimulated with 10 ng/mL IL-4, IL-10, or each in combination with 1 ng/mL IL-1β stimulation. The role of IL-4 and IL-10 in the IVD was evaluated using immunohistochemistry, gene expression, and Luminex multiplex immunoassay proteomics (73 secreted) and phosphoproteomics (21 phosphorylated proteins).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>IL-4, IL-4R, and IL-10R expression and localization in human cartilage endplate tissue were demonstrated for the first time. No significant gene expression changes were noted under IL-4 or IL-10 stimulation. However, IL-1β stimulation significantly increased <i>MMP3</i>, <i>COX2</i>, <i>TIMP1</i>, and TRPV4 expression in NP cells from trauma IVDs. Combined IL-4 and IL-1β treatment induced a significant increase in protein secretion of IL-1α, IL-7, IL-16, IL-17F, IL-18, IFNγ, TNF, ST2, PROK1, bFGF2, and stem cell factor exclusively in NP cells from degenerated IVDs. Conversely, the secretome profile of explants revealed an IL-4–mediated decrease in CXCL13 following treatment with IL-1β. Combined IL-10 and IL-1β treatment increased neurotrophic growth factor secretion compared with IL-10 baseline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The NP cell phenotype affects the pleiotropic role of IL-4, which can induce a pro-inflammatory response in the presence of catabolic stimuli and enhance the effects of IL-1β in degenerated IVDs. Environmental factors, including 3D culture and hypoxia, may alter IL-4's role. Finally, IL-10's potential neurotrophic effects under catabolic stimuli warrant further investigation to clarify its role in IVD degeneration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380207","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":"Annulus Fibrosus Repair via Interpenetration of a Non-Woven Scaffold Supports Tissue Integration and Prevents Re-Herniation","authors":"Esteban D. Ongini,&nbsp;Mohammed Abdullah,&nbsp;Julie B. Engiles,&nbsp;Brianna S. Orozco,&nbsp;Andrea Moehl,&nbsp;Ana Peredo,&nbsp;Sonal Mahindroo,&nbsp;Rachel Hilliard,&nbsp;Thomas P. Schaer,&nbsp;Robert L. Mauck,&nbsp;Harvey E. Smith,&nbsp;Mazda Farshad,&nbsp;Jess G. Snedeker,&nbsp;Sarah E. Gullbrand","doi":"10.1002/jsp2.70045","DOIUrl":"https://doi.org/10.1002/jsp2.70045","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Current surgical management of intervertebral disc herniation often fails to adequately address the risk of recurrence, primarily due to the disc's limited regenerative capacity. Regenerative, biomaterial-based approaches for tissue augmentation, while showing preclinical promise, have consistently failed to meet the extreme mechanical demands of the intervertebral disc, impeding their clinical translation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we introduce a novel annulus repair strategy that employs the mechanical interpenetration of a non-woven PET scaffold into intervertebral disc tissue to resist reherniation. We investigate the efficacy in preventing herniations under compression using a bovine explant model and validate its performance in a pilot in vivo study in a goat cervical spine injury model. Healing and scaffold integration are assessed over 4 weeks using computed tomography, magnetic resonance imaging, and histopathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrate that this approach effectively prevents mechanically induced herniation. In vivo, the scaffold interpenetration enables biological integration at 4 weeks post-surgery, with no evidence of scaffold migration or disc degeneration. The scaffold supports matrix deposition and cell infiltration, with no observed endplate pathologies or osteolysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings highlight a promising combination of biomechanical reliability and favorable histological outcomes, underscoring the potential of this technology for advancing toward human clinical applications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362745","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 Cross-Sectional Areas and Anterior–Posterior Balance of the Cervical Paraspinal Muscles in Dropped Head Syndrome and Cervical Spondylotic Myelopathy: A Propensity Score-Matched Analysis","authors":"Takashi Sono,&nbsp;Kenta Ijiri,&nbsp;Kensaku Kakehi,&nbsp;Soichiro Masuda,&nbsp;Takayoshi Shimizu,&nbsp;Koichi Murata,&nbsp;Shuichi Matsuda,&nbsp;Bungo Otsuki","doi":"10.1002/jsp2.70047","DOIUrl":"10.1002/jsp2.70047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Dropped head syndrome (DHS) is characterized by weakness of the neck extensor muscles. However, few studies have assessed the cross-sectional areas (CSAs) of the cervical paraspinal muscles (CPM) and their anterior–posterior balance in DHS. This study aimed to elucidate the pathognomonic findings of DHS by comparing the CSAs and anterior–posterior balance of the CPM in patients with DHS and cervical spondylotic myelopathy (CSM), using magnetic resonance imaging (MRI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We compared the CSAs and anterior–posterior balance of the CPM in patients with DHS and CSM using MRI. Patients with CSM were selected in an age- and sex-matched manner, using the propensity score. The longus colli (LC) muscle was selected as the anterior muscle; and the semispinalis cervicis (SSC), splenius capitis (SC), and multifidus muscles (MM) were selected as the posterior muscles. We calculated LC/SSC, LC/SC, LC/MM, and LC/(SSC + SC + MM), as indicators of neck muscle balance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The DHS and the CSM cohort comprised 26 and 52 patients, respectively. Both cohorts had a mean age of 71-year-old. There were no significant differences in the CSAs and most of the indicators of neck balance between the two cohorts. However, the LC/SSC was significantly higher in the DHS cohort than that in the CSM cohort (40.3% and 29.1%, respectively; <i>p</i> &lt; 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study highlights a unique anterior–posterior imbalance in the CPM of DHS patients, differing from CSM patients. Strengthening the SSC muscle could be a key to preventing DHS progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080025","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":"Variations in ECM Topography, Fiber Alignment, Mechanical Stiffness, and Cellular Composition Between Ventral and Dorsal Ligamentum Flavum Layers: Insights Into Hypertrophy Pathogenesis","authors":"Ting-Yuan Tu,&nbsp;Yu-Chia Hsu,&nbsp;Chia-En Yang,&nbsp;Yan-Jye Shyong,&nbsp;Cheng-Hsiang Kuo,&nbsp;Yuan-Fu Liu,&nbsp;Shu-Shien Shih,&nbsp;Cheng-Li Lin","doi":"10.1002/jsp2.70033","DOIUrl":"10.1002/jsp2.70033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Previous studies have suggested that changes in the composition of the extracellular matrix (ECM) play a significant role in the development of ligamentum flavum hypertrophy (LFH) and the histological differences between the ventral and dorsal layers of the hypertrophied ligamentum flavum. Although LFH is associated with increased fibrosis in the dorsal layer, comprehensive research exploring the characteristics of the ECM and its mechanical properties in both regions is limited. Furthermore, the distribution of fibrosis-associated myofibroblasts within LFH remains poorly understood. This study aimed to bridge the existing knowledge gap concerning the intricate relationships between ECM characteristics, mechanical properties, and myofibroblast expression in LFH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Histological staining, scanning electron microscopy, and atomic force microscopy were used to analyze the components, alignment, and mechanical properties of the ECM. Immunostaining and western blot analyses were performed to assess the distribution of myofibroblasts in LF tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were notable differences between the dorsal and ventral layers of the hypertrophic ligamentum flavum. Specifically, the dorsal layer exhibited higher collagen content and disorganized fibrous alignment, resulting in reduced stiffness. Immunohistochemistry analysis revealed a significantly greater presence of α-smooth muscle actin (αSMA)-stained cells, a marker for myofibroblasts, in the dorsal layer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study offers comprehensive insights into LFH by elucidating the distinctive ECM characteristics, mechanical properties, and cellular composition disparities between the ventral and dorsal layers. These findings significantly enhance our understanding of the pathogenesis of LFH and may inform future research and therapeutic strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065660","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":"Explorative Study of Modulatory Effects of Notochordal Cell-Derived Extracellular Vesicles on the IL-1β-Induced Catabolic Cascade in Nucleus Pulposus Cell Pellets and Explants","authors":"J. C. van Maanen,&nbsp;F. C. Bach,&nbsp;J. W. Snuggs,&nbsp;K. Ito,&nbsp;M. H. M. Wauben,&nbsp;C. L. Le Maitre,&nbsp;M. A. Tryfonidou","doi":"10.1002/jsp2.70043","DOIUrl":"10.1002/jsp2.70043","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Cell-free regenerative strategies, such as notochordal cell (NC)-derived extracellular vesicles (EVs), are an attractive alternative in developing new therapies for intervertebral disc (IVD) degeneration. NC-EVs have been reported to elicit matrix anabolic effects on nucleus pulposus cells from degenerated IVDs cultured under basal conditions. However, the degenerative process is exacerbated by pro-inflammatory cytokines contributing to the vicious degenerative cycle. Therefore, this study explores whether NC-EVs modulate interleukin (IL)-1β-mediated pro-inflammatory responses in the degenerating disc.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study utilized two IL-1β induced pro-catabolic culture models; a dog 3D nucleus pulposus (NP) cell pellet culture and a human patient-derived, ex vivo NP tissue culture system. Porcine NC-EVs were generated from NC-conditioned medium by differential centrifugation followed by size exclusion chromatography. Donor matched EV-depleted media were generated by overnight ultracentrifugation, whereafter the EV-depleted NCCM supernatant was subjected to size exclusion chromatography. To investigate whether observed effects were EV-associated, NC-EVs conditions were compared to EV-depleted controls in the absence and presence of IL-1β.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The size and concentration of NC-EVs were quantified by nanoparticle tracking analysis, which showed minimal donor variation and confirmed depletion of EVs in the EV-depleted media. In the IL-1β-induced catabolic cascade, the NC-EVs did not elicit anabolic effects at the matrix level nor did they rescue the pro-catabolic phenotype within dog pellets. Modification of the CCL2 secretion seemed to be context dependent in the human explants: where EVs treatment stimulated CCL2 secretion but in the presence of IL-1β this effect was counteracted. Secretion of IL-6 and C-X-C motif chemokine ligand 1 was significantly decreased in NC-EV + IL-1β vs. control+IL-1β but not compared to EV-depleted human explant controls. Altogether, this data provides evidence for a protective modulatory role of NC-EVs. Considering the homeostatic function EVs exert, inherently encompassing subtle biologic modifications, the current study may have lacked sufficient power to demonstrate statistical significance in a sample set with evident donor variation.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;NC-EVs may modulate the production of specific cytokines and chemokines in human degenerate explants when the key pro-i","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065634","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}