JOR Spine最新文献

{"title":"Targeting nucleus pulposus cell death in the treatment of intervertebral disc degeneration","authors":"Hong Sun,&nbsp;Jiajie Guo,&nbsp;Zhilin Xiong,&nbsp;Yong Zhuang,&nbsp;Xu Ning,&nbsp;Miao Liu","doi":"10.1002/jsp2.70011","DOIUrl":"https://doi.org/10.1002/jsp2.70011","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IDD) is a progressive age-related disorder characterized by the reduction in the number of nucleus pulposus cells (NPCs) and degradation of extracellular matrix (ECM), thereby leading to chronic pain and disability. The pathogenesis of IDD is multifaceted, and current therapeutic strategies remain limited. The nucleus pulposus (NP), primarily composed of NPCs, proteoglycans, and type II collagen, constitutes essential components for maintaining intervertebral disc (IVD) function and spinal motion. The disturbed homeostasis of NPCs is closely associated with IDD. Accumulating evidence increasingly suggests the crucial role of programmed cell death (PCD) in regulating the homeostasis of NPCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This review aimed to elucidate various forms of PCD and their respective roles in IDD, and investigate diverse strategies targeting the cell death of NPCs for IDD treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials &amp; Methods</h3>\u0000 \u0000 <p>We collected the relevant literature regarding PCD and their roles in the development of IDD. Subsequently, we comprehensively summarized the intricate association between PCD and IDD, and also explored the potential and application of cell therapy and traditional Chinese medicine (TCM) in the prevention and treatment of IDD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Current literature indicated that the PCD of NPCs was closely associated with the pathogenesis of IDD. Additionally, the development of targeted pharmaceuticals based on the mechanisms of PCD could effectively impede the loss of NPCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This review demonstrated that targeting the PCD of NPCs may be a promising strategy for the treatment of IDD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142861580","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 genetic causal association between arthritis and low back pain","authors":"Aimin Gong,&nbsp;Daniel Yang,&nbsp;Mengjie Zeng","doi":"10.1002/jsp2.70023","DOIUrl":"10.1002/jsp2.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Arthritis and low back pain (LBP) are prevalent musculoskeletal conditions with a perceived association. Previous observational studies have suggested a possible link between arthritis and LBP, but causality has not been firmly established.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The analysis involved data from a meta-analysis of genome-wide association studies sourced from the UK Biobank Genetics resources on rheumatoid arthritis (RA), osteoarthritis (OA) at any site, knee osteoarthritis (KOA), hip osteoarthritis (HOA), and LBP. Two-sample Mendelian randomization analysis was utilized to evaluate the causal link between arthritis and LBP. The primary method employed was inverse-variance weighting (IVW), with additional techniques such as MR-Egger, weighted median, Cochran <i>Q</i> statistic, and leave-one-out analysis used to identify heterogeneity and pleiotropy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Genetically determined RA exhibited a causal impact on LBP (Weighted median: odds ratio [OR] = 1.094, 95% confidence interval [CI] 1.002–1.195, <i>p</i> = 0.043). Furthermore, OA at any site and KOA showed causal associations with LBP (Inverse variance weighted: OR = 1.089, 95% CI 1.011–1.173, <i>p</i> = 0.026) and (OR = 1.0004, 95% CI 1.000–1.008, <i>p</i> = 0.019), respectively. Additionally, HOA was also linked causally with an elevated risk of developing LBP (Weighted median: OR = 1.002, 95% CI 1.000–1.004, <i>p</i> = 0.049; Inverse variance weighted: OR = 1.002, 95% CI 1.001–1.004, <i>p</i> = 0.003).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study offers genetic evidence supporting the causal relationship between RA, OA at any site, KOA, HOA and the increased risk of LBP, especially highlighting the significant impact of HOA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828780","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":"Exploring the therapeutic potential of puerarin on intervertebral disc degeneration by regulating apoptosis of nucleus pulposus cells","authors":"Xiaoqiang Wang,&nbsp;Chao Song,&nbsp;Daqian Zhou,&nbsp;Yongliang Mei,&nbsp;Weiye Cai,&nbsp;Rui Chen,&nbsp;Jiale Lv,&nbsp;Houyin Shi,&nbsp;Zongchao Liu","doi":"10.1002/jsp2.70020","DOIUrl":"10.1002/jsp2.70020","url":null,"abstract":"<p>Intervertebral disc degeneration (IVDD) stands as a prevalent chronic orthopedic ailment, profoundly impacting patients' well-being due to incapacitating low back pain. Studies have highlighted a close correlation between IVDD and the programmed cell death of nucleus pulposus (NP) cells orchestrated by interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and caspase-3 (CASP3). Puerarin, renowned for its anti-inflammatory attributes and its influence on IL-1β and TNF-α, emerges as a promising candidate for IVDD treatment. However, the precise mechanism by which it regulates apoptosis via these pathways remains ambiguous. This investigation utilizes bioinformatics to unveil the molecular intricacies of puerarin-mediated apoptosis regulation in IVDD, substantiated by preliminary in vitro experiments. Analysis exposes aberrant expression of pivotal apoptosis-associated proteins (IL-1β, TNF-α, CASP3, CASP8, and BCL2) in IVDD patients, with network pharmacology indicating puerarin's potential efficacy in IVDD treatment by modulating apoptosis and cellular senescence pathways. Further experiments elucidate puerarin's capacity to stimulate NP cell proliferation while inhibiting apoptosis, potentially contributing to IVDD mitigation. Western blot and PCR outcomes reveal escalated expression of apoptosis-related proteins (IL-1β, TNF-α, and CASP3) in lipopolysaccharide-treated NPCs, ameliorated by puerarin intervention. Molecular docking simulations demonstrate favorable binding properties of puerarin with apoptotic proteins, while flow cytometry analysis indicates its ability to diminish NPC apoptosis. These discoveries imply that puerarin might alleviate NPC apoptosis by modulating key targets, thereby potentially ameliorating IVDD. In summary, this study unveils the intrinsic mechanism of puerarin in regulating NPC apoptosis to alleviate IVDD, underscoring its therapeutic promise.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813220","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":"Investigating the causal links between inflammatory cytokines and scoliosis through bidirectional Mendelian randomization analysis","authors":"Muradil Mardan,&nbsp;Mardan Mamat,&nbsp;Parhat Yasin,&nbsp;Xiaoyu Cai,&nbsp;Huoliang Zheng,&nbsp;Qingyin Xu,&nbsp;Shaokuan Song,&nbsp;Bo Li,&nbsp;Hao Cai,&nbsp;Pengbo Chen,&nbsp;Zeyu Lu,&nbsp;Shahna Omar,&nbsp;Shengdan Jiang,&nbsp;Leisheng Jiang,&nbsp;Xin-feng Zheng","doi":"10.1002/jsp2.70019","DOIUrl":"10.1002/jsp2.70019","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Scoliosis, characterized by a lateral curvature of the spine, affects millions globally. The role of inflammatory cytokines in the pathogenesis of scoliosis is increasingly acknowledged, yet their causal relationships remain poorly defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aims to explore the genetic-level causal relationships between inflammatory cytokines and scoliosis utilizing bidirectional Mendelian randomization (MR) analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This study leverages genetic data from public Genome-Wide Association Studies (GWAS). Bidirectional MR was employed to investigate the causal relationships between 44 inflammatory cytokines and scoliosis. The inflammatory cytokine data include 8293 Finnish individuals, while the scoliosis data consist of 165 850 participants of European descent, including 1168 scoliosis cases and 164 682 controls. Causal links were assessed using the inverse variance-weighted method, supplemented by MR-Egger, weighted median, and weighted mode analyses. Heterogeneity and pleiotropy were assessed using standard tests, with sensitivity analysis conducted through leave-one-out analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our analysis demonstrated a significant causal association between the cytokine Resistin (RETN) and the development of scoliosis (<i>p</i> = 0.024, OR 95% CI = 1.344 [1.039–1.739]). No other cytokines among the 44 studied showed significant associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>The findings highlight the critical role of RETN in scoliosis progression and underscore the complex interplay of genetic and inflammatory pathways. Further research is needed to explore additional biomarkers and their mechanisms in scoliosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provides evidence of a significant causal relationship between RETN and scoliosis, emphasizing its potential as a therapeutic target. These findings contribute to understanding scoliosis pathogenesis and pave the way for future research on inflammation-related pathways and therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813222","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":"Clinical efficacy and biomechanical analysis of a novel hollow pedicle screw combined with kyphoplasty for the treatment of Kümmell disease","authors":"Shixiao Zhong,&nbsp;Hui Zhong,&nbsp;Kun Huang,&nbsp;Yayu Zhao,&nbsp;Wen Lei,&nbsp;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> &lt; 0.05). The AVH, BCA, and WCA significantly improved initially after the surgery in both groups (<i>p</i> &lt; 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,&nbsp;Wenyuan Sui,&nbsp;Wenhua Mao,&nbsp;Junlin Yang,&nbsp;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>² = 0.282, <i>p</i> = 0.006), bilateral paraspinal muscle CSA ratio (<i>r</i>² = 0.253, <i>p</i> = 0.011), and bilateral fatty component ratio (<i>r</i>² = 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&gt;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}

{"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 Tang⁸”:</p><p>⁸Department of Medical Imaging and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan.</p><p>Correct affiliation for the author “Yu-Hsuan Tang⁹” should be verified as following in the page 1:</p><p>⁹Department 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}

{"title":"The effects of extracellular matrix-degrading enzymes polymorphisms on intervertebral disc degeneration","authors":"Di Zhao,&nbsp;Yao-xing Dou,&nbsp;Ling-feng Zeng,&nbsp;Yan-hong Han,&nbsp;Fang-zheng Lin,&nbsp;Nan-jun Xu,&nbsp;Jun Liu,&nbsp;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}

{"title":"Effect of cigarette smoke exposure and cessation on regional diffusion properties in rat intervertebral discs","authors":"Joshua Kelley,&nbsp;Nathan Buchweitz,&nbsp;Avery Madden,&nbsp;Hongming Fan,&nbsp;Glenn Hepfer,&nbsp;Michael Kern,&nbsp;Danyelle M. Townsend,&nbsp;Tong Ye,&nbsp;Hai Yao,&nbsp;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}

{"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,&nbsp;Robert Sneath,&nbsp;Aprajay Golash,&nbsp;Parag Desai,&nbsp;Duncan McHale,&nbsp;Sarah Guest,&nbsp;Charlie Brindley,&nbsp;Paul Cummings,&nbsp;Shane Smith,&nbsp;Conrad Stroud,&nbsp;Graham Scott,&nbsp;Steve Ruston,&nbsp;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>_max of 1300 ng/mL at 7.27 h post-administration. The linezolid plasma <i>C</i>_max 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}