JOR SpinePub Date : 2024-12-06DOI: 10.1002/jsp2.70017
Shixiao Zhong, Hui Zhong, Kun Huang, Yayu Zhao, Wen Lei, Weichao Li
{"title":"Clinical efficacy and biomechanical analysis of a novel hollow pedicle screw combined with kyphoplasty for the treatment of Kümmell disease","authors":"Shixiao Zhong, Hui Zhong, Kun Huang, Yayu Zhao, Wen Lei, Weichao Li","doi":"10.1002/jsp2.70017","DOIUrl":"10.1002/jsp2.70017","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Vertebral augmentation is the preferred treatment for Kümmell disease (KD), but there exists a risk of cement displacement resulting in severe back pain and exacerbation of kyphosis. The study aimed to investigate the efficacy and safety of a novel hollow pedicle screw combined with kyphoplasty (HPS-KP) for treating KD, effectively preventing postoperative bone cement displacement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The prospective study included 50 KD patients with no neurological deficit detected during clinical and radiological evaluation who underwent HPS-KP (<i>n</i> = 25) and PKP (<i>n</i> = 25) surgeries. The visual analogue scale (VAS) score, Oswestry dysfunction index (ODI), anterior vertebral height (AVH), wedge-shape affected vertebral Cobb angle (WCA), bisegmental Cobb angle (BCA), and complications were evaluated and compared in both groups. Besides, a finite element (FE) model of T11-L2 was constructed. The stress distributions, maximum von Mises stresses of vertebrae and bone cement, and maximum displacement of bone cement were compared and analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The VAS and ODI scores at 3 days, 3 and 6 months, and 1 year after surgery significantly improved in both groups (<i>p</i> < 0.05). The AVH, BCA, and WCA significantly improved initially after the surgery in both groups (<i>p</i> < 0.05). The displacement of M2 was larger than other models, especially in flexion, right bending, and left and right rotation, while that of M6 was the lowest under all conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>HPS-KP was a safe and effective treatment for KD, effectively relieving pain, restoring vertebral height, and correcting local kyphosis, and it had better biomechanical stability and safety than ordinary single PKP and PKP combined with pediculoplasty in avoiding cement loosening and displacement.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11622290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800874","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":"Distinct clinical characteristics of adolescent idiopathic scoliosis with asymmetrical ESR1 expression in paraspinal muscle progenitor cells","authors":"Hanlong Xin, Wenyuan Sui, Wenhua Mao, Junlin Yang, Xiexiang Shao","doi":"10.1002/jsp2.70018","DOIUrl":"https://doi.org/10.1002/jsp2.70018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Previous studies found decreased ESR1 expression of concave paraspinal muscle progenitor cells could contribute to the initiation and progression of adolescent idiopathic scoliosis (AIS). The current study investigated the clinical characteristics of AIS with asymmetrical ESR1 expression in paraspinal muscle progenitor cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Bilateral deep paraspinal muscle progenitor cells were obtained from 25 consecutive eligible female patients with AIS. RT-qPCR was performed to evaluate the expression of ESR1. The demographic data (the age at surgery, height, weight, BMI, and age at initiation), posteroanterior and lateral radiographs data (Risser sign, Cobb angle, apical vertebral rotation, and location of apical vertebra), and MR imaging data (bilateral paraspinal muscle CSA ratio and bilateral fatty component ratio) were collected. The correlation between asymmetrical ESR1 expression of paraspinal muscle progenitor cells and the aforementioned clinical characteristics were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twelve out of twenty-five patients (48%) showed bilateral ESR1 expression ratio (convex/concave) more than 1.5 folds, and they were divided into the ESR1 asymmetry group. When compared with the ESR1 symmetry group, patients in the ESR1 asymmetry group showed significantly more severe scoliosis (<i>p</i> = 0.041), more hypoplastic concave paraspinal muscle (<i>p</i> = 0.015), and more muscular fatty infiltration in the concave side (<i>p</i> = 0.034). The bilateral ESR1 expression ratio was significantly correlated with Cobb angle (<i>r</i><sup>2</sup> = 0.282, <i>p</i> = 0.006), bilateral paraspinal muscle CSA ratio (<i>r</i><sup>2</sup> = 0.253, <i>p</i> = 0.011), and bilateral fatty component ratio (<i>r</i><sup>2</sup> = 0.248, <i>p</i> = 0.011).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>There were 48% of AIS patients with significantly decreased ESR1 expression in concave paraspinal muscle progenitor cells (convex/concave>1.5 folds), while patients with more asymmetrical ESR1 expression showed more hypoplastic paraspinal muscle and fatty infiltration on the concave side, and more severe scoliotic deformity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724234","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 : 2024-11-26DOI: 10.1002/jsp2.70013
{"title":"Correction to “Development and validation of deep learning models for identifying the brand of pedicle screws on plain spine radiographs”","authors":"","doi":"10.1002/jsp2.70013","DOIUrl":"10.1002/jsp2.70013","url":null,"abstract":"<p>Yao YC, Lin CL, Chen HH, et al. Development and validation of deep learning models for identifying the brand of pedicle screws on plain spine radiographs. <i>JOR Spine</i>. 2024;7(3):e70001.</p><p>The affiliation of one of the authors (Yu-Hsuan Tang) should be verified in the first page (1 of 13).</p><p>Incorrect affiliation was investigated for the author “Yu-Hsuan Tang<sup>8</sup>”:</p><p><sup>8</sup>Department of Medical Imaging and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan.</p><p>Correct affiliation for the author “Yu-Hsuan Tang<sup>9</sup>” should be verified as following in the page 1:</p><p><sup>9</sup>Department of Life Science, National Yang Ming Chiao Tung University, Taipei, Taiwan.</p><p>We apologize for this error.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11597498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142728765","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 : 2024-11-20DOI: 10.1002/jsp2.70012
Di Zhao, Yao-xing Dou, Ling-feng Zeng, Yan-hong Han, Fang-zheng Lin, Nan-jun Xu, Jun Liu, Yu-ping Zeng
{"title":"The effects of extracellular matrix-degrading enzymes polymorphisms on intervertebral disc degeneration","authors":"Di Zhao, Yao-xing Dou, Ling-feng Zeng, Yan-hong Han, Fang-zheng Lin, Nan-jun Xu, Jun Liu, Yu-ping Zeng","doi":"10.1002/jsp2.70012","DOIUrl":"https://doi.org/10.1002/jsp2.70012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of the current study was to investigate the correlation between polymorphisms in extracellular matrix-degrading enzymes and the risk of intervertebral disc degeneration (IDD) diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The databases PubMed, Embase, and Cochrane Database were systematically queried from the inception until March 2023 to ascertain studies that meet the eligibility criteria. Utilizing a standardized data collection form to extract data from individual studies. The data were quantified using odds ratio (OR) along with its corresponding 95% confidence interval (95% CI), following an allelic model of inheritance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study included a total of nine studies and indicated that the presence of rs17576 in the MMP9 gene was significantly associated with an increased risk of IDD diseases (GG: 1.30, 95% CI [1.09–1.55], <i>p</i> = 0.004). The presence of other polymorphisms in extracellular matrix-degrading enzymes did not exhibit a significant association with the susceptibility to IDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The current study demonstrated a noteworthy correlation between the GG genotype of MMP-9 rs17576 and susceptibility to IDD. The available evidence is insufficient to substantiate the correlation between other extracellular matrix-degrading enzymes and susceptibility to IDD. The constraints of this analysis necessitate further research involving larger sample sizes across diverse ethnicities to provide a comprehensive understanding of the true impact of these polymorphisms on susceptibility to IDD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142679922","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 : 2024-11-14DOI: 10.1002/jsp2.70015
Joshua Kelley, Nathan Buchweitz, Avery Madden, Hongming Fan, Glenn Hepfer, Michael Kern, Danyelle M. Townsend, Tong Ye, Hai Yao, Yongren Wu
{"title":"Effect of cigarette smoke exposure and cessation on regional diffusion properties in rat intervertebral discs","authors":"Joshua Kelley, Nathan Buchweitz, Avery Madden, Hongming Fan, Glenn Hepfer, Michael Kern, Danyelle M. Townsend, Tong Ye, Hai Yao, Yongren Wu","doi":"10.1002/jsp2.70015","DOIUrl":"10.1002/jsp2.70015","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cigarette smoking is a recognized risk factor for orthopedic disorders, particularly intervertebral disc (IVD) degenerative disease. However, the IVD pathophysiology, especially the spatial–temporal remodeling progression in the context of cigarette smoking, remains unclear. This study aimed to address this knowledge gap through a quantitative assessment of IVD structural composition and diffusion properties using a Sprague–Dawley rat model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-four rats were divided into control and smoke exposure cohorts, each with two sub-groups of six rats. One smoke exposure sub-group was sacrificed after 2 months of daily cigarette smoke exposure in a custom smoking apparatus, while the other was sacrificed after an additional 5 months of smoke cessation. The control groups were age-matched to the smoke exposure groups. A fluorescent recovery after photobleaching (FRAP) technique was used to determine solute diffusivities and multi-photon excitation (MPE) imaging was performed to characterize structural changes in the annulus fibrosus (AF), nucleus pulposus (NP), and cartilage endplate (CEP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A decrease in diffusivity was observed in the CEP and the AF (radial direction only) after 2 months of smoke exposure. MPE imaging showed aberrant CEP calcification and reduced AF radial collagen fiber bundle diameter, suggesting that the IVD exhibits regionally dependent structural remodeling due to smoke exposure. Furthermore, the smoke cessation group showed deteriorating alterations of structure and diffusivities in all three-disc regions, including the NP, indicating that five-month smoke cessation alone didn't reverse the progression of IVD degenerative remodeling during aging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study advances the understanding of IVD pathophysiology in the context of cigarette smoke exposure and cessation, laying the groundwork for potential earlier diagnosis and optimized interventions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620588","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 : 2024-11-14DOI: 10.1002/jsp2.70009
Shiva S. Tripathi, Robert Sneath, Aprajay Golash, Parag Desai, Duncan McHale, Sarah Guest, Charlie Brindley, Paul Cummings, Shane Smith, Conrad Stroud, Graham Scott, Steve Ruston, Lloyd Czaplewski
{"title":"Pharmacokinetics of PP353, a formulation of linezolid for intervertebral disc administration, in patients with chronic low back pain and Modic change Type 1: A first-in-human, Phase 1b, open-label, single-dose study","authors":"Shiva S. Tripathi, Robert Sneath, Aprajay Golash, Parag Desai, Duncan McHale, Sarah Guest, Charlie Brindley, Paul Cummings, Shane Smith, Conrad Stroud, Graham Scott, Steve Ruston, Lloyd Czaplewski","doi":"10.1002/jsp2.70009","DOIUrl":"10.1002/jsp2.70009","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bacterial infection of the intervertebral disc is difficult to treat because the tissue is usually not vascularized and systemic antibiotic therapy may not reach optimal antibacterial exposure. Here we characterize the safety, tolerability, and pharmacokinetics of PP353, a suspension of micronized linezolid, formulated for direct intervertebral disc administration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The safety, tolerability, and pharmacokinetics of an intradiscal administration of PP353, was assessed in Part A of a Phase 1b study and consisted of a single injection of study drug (3 mL of PP353 and 150 mg linezolid). Clinical assessment included initial safety and tolerability of PP353 with continued follow-up for 12 months. Assessment of linezolid concentration in plasma samples enabled characterization of the pharmacokinetics. Deconvolution of systemic linezolid was used to estimate intervertebral disc linezolid concentration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Intradiscal administration of 3 mL of PP353 (linezolid 50 mg/mL) to the nucleus pulposus was well tolerated with no reported study treatment-related severe or serious adverse events and resulted in an average geometric mean linezolid plasma <i>C</i><sub>max</sub> of 1300 ng/mL at 7.27 h post-administration. The linezolid plasma <i>C</i><sub>max</sub> observed with intradiscal PP353 is approximately 10% that observed with a standard oral or iv administration of 600 mg linezolid. Pharmacokinetic deconvolution estimated that a single dose of PP353 (150 mg linezolid) provided intradiscal bactericidal concentration of linezolid for 96 h and bacteriostatic exposure for up to 120 h after dosing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Intradiscal administration of 3 mL of PP353 is well-tolerated and based on the pharmacokinetics following a single injection, a two-dose regimen of PP353 (150 mg linezolid) on Day 1 and Day 5 ± 1 was selected to explore safety, tolerability, pharmacokinetics, and efficacy in Part B of the Persica 002 study.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620700","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 : 2024-11-14DOI: 10.1002/jsp2.70010
Graham Hagger, Sarah Guest, Stephen Birchall, Alys Bradley, Charlie Brindley, David Corbett, Paul J. Cummings, Cristina Freire, James Harris, Andrew Wise, Melanie Wood, Lloyd G. Czaplewski
{"title":"Preclinical development and characterisation of PP353, a formulation of linezolid for intradiscal administration","authors":"Graham Hagger, Sarah Guest, Stephen Birchall, Alys Bradley, Charlie Brindley, David Corbett, Paul J. Cummings, Cristina Freire, James Harris, Andrew Wise, Melanie Wood, Lloyd G. Czaplewski","doi":"10.1002/jsp2.70010","DOIUrl":"10.1002/jsp2.70010","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Bacterial infection of the intervertebral disc can lead to vertebral endplate edema known as Modic changes, with associated chronic low back pain. Oral antimicrobial therapy has shown efficacy but relies on prolonged dosing and may not be optimal in terms of patient outcome, side effects, or antibiotic stewardship. There is no antibiotic formulation approved for intradiscal administration. Here, we describe the development and preclinical characterization of a formulation of linezolid, a suspension of 50 mg/mL micronized powder, for intradiscal administration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Micronization, particle size analysis, Franz cell diffusion assays, ex vivo bioassay, and estimates of gelling temperature were used to optimize the composition and properties of the formulation. Performance of the formulation was assessed using sheep to characterize the pharmacokinetics and a model of intradiscal infection was developed to demonstrate efficacy. Suitability for human administration was demonstrated in a Good Laboratory Practice (GLP) local tolerance study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Micronized linezolid, formulated as a powder suspension using a vehicle containing poloxamer 407 and iohexol, provided a temperature-dependent radio-opaque gel that was suitable for image-guided percutaneous intradiscal administration. Efficacy in a sheep model of intradiscal <i>Staphylococcus aureus</i> infection was demonstrated. The formulation provides a high level of sheep disc tissue exposure, with C<sub>max</sub> of 6500 μg/g and limited systemic exposure, with a plasma C<sub>max</sub> of 0.04 μg/mL per 0.1 mL dose (5 mg of linezolid). Deconvolution of plasma linezolid pharmacokinetics correlated with linezolid remaining in the disc over time. Observations from a GLP local tolerance study with the linezolid formulation were of a minor nature and related to the intradiscal administration procedure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Linezolid can be formulated for image-guided percutaneous intradiscal administration. The formulation is now in a Phase 1b clinical trial to evaluate safety, pharmacokinetics, and efficacy in patients with CLBP and suspected bacterial infection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620707","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":"Melatonin attenuates degenerative disc degression by downregulating DLX5 via the TGF/Smad2/3 pathway in nucleus pulposus cells","authors":"Kuibo Zhang, Hua Wang, Ling Mo, Xiaohui Huang, Chao Yuan, Caijun Liu","doi":"10.1002/jsp2.70014","DOIUrl":"10.1002/jsp2.70014","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IVDD) is the leading cause of low back pain, and apoptosis plays a key role in its pathogenesis. Distal-less homeobox 5 (Dlx5) has been reported to induce cell apoptosis. Melatonin, as a powerful antiapoptotic agent, has been widely reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study aimed to investigate the role of DLX5 in the pathogenesis of IVDD and the potential therapeutic role of melatonin in targeting DLX5 in IVDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials & Methods</h3>\u0000 \u0000 <p>Western blotting, RT–qPCR, immunohistochemistry, si-DLX5, Ex-DLX5, flow cytometry, and immunofluorescence were used to examine the regulatory effect of DLX5 on apoptosis. Therapeutic efficacy was assessed by the intraperitoneal injection of melatonin into IVDD mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The expression level of DLX5 is significantly increased in IVDD, and the expression levels were positively correlated with the grade of IVDD. DLX5 was significantly upregulated in TNF-α-induced degenerative NP cells. Degenerative NP cells transfected with si-DLX5 exhibited significantly less apoptosis than control cells. Melatonin significantly alleviated IVDD in surgically induced IVDD model mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>The results revealed that the expression of DLX5 was positively correlated with the severity of IVDD and that melatonin ameliorated DLX5-induced apoptosis and extracellular matrix imbalance by inhibiting the TGF-β/Smad signaling pathway. This study may provide therapeutic strategies to alleviate inflammation-induced apoptosis IVDD-associated inflammation-induced apoptosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>DLX5 plays an important role in IVDD progression by promoting apoptosis, and melatonin represents a promising therapeutic strategy for alleviating IVDD-associated inflammation and apoptosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620604","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 : 2024-11-05DOI: 10.1002/jsp2.70007
Li Li, Hadil Al-Jallad, Aiwei Sun, Miltiadis Georgiopoulos, Rakan Bokhari, Jean Ouellet, Peter Jarzem, Hosni Cherif, Lisbet Haglund
{"title":"The proteomic landscape of extracellular vesicles derived from human intervertebral disc cells","authors":"Li Li, Hadil Al-Jallad, Aiwei Sun, Miltiadis Georgiopoulos, Rakan Bokhari, Jean Ouellet, Peter Jarzem, Hosni Cherif, Lisbet Haglund","doi":"10.1002/jsp2.70007","DOIUrl":"10.1002/jsp2.70007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Extracellular vesicles (EVs) function as biomarkers and are crucial in cell communication and regulation, with therapeutic potential for intervertebral disc (IVD)-related low back pain (LBP). EV cargo is often affected by tissue health, which may affect the therapeutic potential. There is currently limited knowledge of how the cargo of IVD cell-derived EVs varies with tissue health and how differences in proteomic profile affect the predicted biological functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Our study purified EVs from human IVD cell conditioned media by size-exclusion chromatography. Nanoparticle tracking analysis was conducted to measure EV size and concentration. Transmission electron microscopy and Western blot were performed to examine EV structure and markers. Tandem mass tag-mass spectrometry was conducted to determine protein cargo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Most EVs were exosomes and intermediate microvesicles with an increasing amount linked to disease progression. Of the proteins detected, 88.6% were shared across the non-degenerate, mildly-degenerate, and degenerate samples. GO and KEGG analyses revealed that cargo from the mildly-degenerate samples was the most distinct, with the proteins in high abundance strongly associated with extracellular matrix (ECM) organization and structure. Shared proteins, highly expressed in the non-degenerate and degenerate samples, showed strong associations with cell adhesion, ECM–receptor interaction, and vesicle-mediated transport, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings indicate that EVs from IVD cells from tissue with different degrees of degeneration share a majority of the cargo proteins. However, the level of expression differs with degeneration grade. Cargo from the mildly-degenerate samples exhibits the most differences. A better understanding of changes in EV cargo in the degenerative process may provide novel information related to molecular mechanisms underlying IVD degeneration and suggest new potential treatment modalities for IVD-related LBP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590605","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 : 2024-10-31DOI: 10.1002/jsp2.70008
Weishi Liang, Duan Sun, Bo Han, Yihan Yang, Peng Yin, Yong Hai
{"title":"Finite element analysis of two-level discontinuous cervical hybrid revision surgery strategy to reduce biomechanical responses of adjacent segments","authors":"Weishi Liang, Duan Sun, Bo Han, Yihan Yang, Peng Yin, Yong Hai","doi":"10.1002/jsp2.70008","DOIUrl":"10.1002/jsp2.70008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hybrid surgery (HS) combined cervical disc arthroplasty (CDA) with anterior cervical discectomy and fusion (ACDF) is emerging, but its biomechanical effects as a revision surgery (RS) on adjacent segments were unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This finite element (FE) study aimed to investigate the biomechanical characteristics of HS to treat two-level discontinuous ASD in ACDF RS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A C2-T1 intact FE model was established and modified to a primary C5/6 ACDF model and five RS models. These RS models' segments C4/5 and C6/7 were revised using cage plus plate (C), zero-profile devices (P), and Bryan disc (D), respectively, generating C-C-C, P-C-P, D-C-P, P-C-D, and D-C-D models. In the intact and C5/6 ACDF models, a 1.0 Nm moment was used to produce the range of motion (ROM). A displacement load was applied to all RS models, to achieve a total ROM match that of the primary C5/6 ACDF model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the P-C-P model, biomechanical responses including ROM, Intradiscal pressure (IDP), Facet joint force (FJF), and Maximum von Mises stresses of discs at segments C3/4 and C7/T1 were slightly lower than the C-C-C model. The biomechanical response parameters at segments C3/4 and C7/T1 of P-C-D, D-C-P, and D-C-D were smaller than those in C-C-C and P-C-P models. D-C-D had the most significant effect on reducing all biomechanical responses among all RS models in segments C3/4 and C7/T1. Moreover, the disc stress cloud maps showed that the maximum von Mises stress of the C3/4 disc was higher than that of C7/T1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>D-C-D, P-C-D, and D-C-P are good RS choices for reducing the biomechanical responses, and D-C-D was the best choice. P-C-P can be the best recommendation when it does not meet the CDA indications. This study provided a biomechanical reference for hybrid surgical decision-making in the ACDF RS for preventing ASD recurrence.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557784","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}