JOR Spine最新文献

{"title":"In vitro and ex vivo screening of microRNA combinations with enhanced cell penetrating peptides to stimulate intervertebral disc regeneration","authors":"Tara Ní Néill,&nbsp;Marcos N. Barcellona,&nbsp;Niamh Wilson,&nbsp;Fergal J. O'Brien,&nbsp;James E. Dixon,&nbsp;Caroline M. Curtin,&nbsp;Conor T. Buckley","doi":"10.1002/jsp2.1366","DOIUrl":"10.1002/jsp2.1366","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Low back pain (LBP) is predominantly caused by degeneration of the intervertebral disc (IVD) and central nucleus pulposus (NP) region. Conservative treatments fail to restore disc function, motivating the exploration of nucleic acid therapies, such as the use of microRNAs (miRNAs). miRNAs have the potential to modulate expression of discogenic factors, while silencing the catabolic cascade associated with degeneration. To deliver these miRNAs, nonviral cell penetrating peptides (CPPs) are gaining favor given their low immunogenicity and strong targeting ability. Single miRNA therapies have been investigated for IVD repair, however dual miRNA delivery strategies have not been commonly examined and may augment regeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and methods</h3>\u0000 \u0000 <p>Transfection of four pro-discogenic miRNAs (miRNA mimics:140-5p; 149-5p and inhibitors: 141-3p; 221-3p) and dual delivery of six miRNA pairings was performed using two CPPs, RALA and GET peptide (FLR), in primary rat NP monolayer culture, and in an ex vivo organ culture model of rat caudal discs. Protein expression of discogenic (aggrecan, collagen type II, and SOX9) and catabolic markers (ADAMTS5 and MMP13) were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Monolayer investigations signified enhanced discogenic marker expression following dual miRNA delivery, signifying a synergistic effect when compared to single miRNA transfection. Utilization of an appropriate model was emphasized in our ex vivo organ culture experiment, revealing the establishment of a regenerative microenvironment characterized by reduced catabolic enzyme activity and enhanced matrix deposition, particularly following concurrent delivery of FLR-miRNA-149-5p mimic and miRNA-221-3p inhibitor. Bioinformatics analysis of miRNA-149-5p mimic and miRNA-221-3p inhibitor identified distinct targets, pathways, and interactions, suggesting a mode of action for this amplified response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest the potential of FLR-miRNA-149-5p + miRNA-221-3p inhibitor to create an anti-catabolic niche within the disc to foster regeneration in moderate cases of disc degeneration, which could be utilized in further studies with the overarching aim of developing treatments for LBP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894561","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":"How to improve the mechanical safety of a novel spinal implant while saving costs and time","authors":"Annette Kienle,&nbsp;Hans-Joachim Wilke,&nbsp;Christian Schröder,&nbsp;Andrea Pietsch","doi":"10.1002/jsp2.70026","DOIUrl":"10.1002/jsp2.70026","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spinal implant failure is associated with prolonged patient suffering, high costs for the medical device industry, and a high economic burden for the health care system. Pre-clinical mechanical testing has great potential to reduce the risk of such failure. However, there are no binding regulations for planning and interpretation of mechanical testing. Therefore, different strategies exist. Mainly for novel implants an option is to start with a structured scientific literature search that forms an objective background for the definition of an implant-specific test plan, the derivation of acceptance criteria and interpretation of the test results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This paper describes, how a literature-based approach can look like from the initial literature search through the derivation of the test plan and the acceptance criteria, to the final test result evaluation and how this approach can support the proof that the device meets all necessary safety and performance standards.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The main advantage of this literature-based approach is that testing and test result interpretation are linked with the loads acting on the individual implant in vivo. In an ideal case, testing is focused on the individual implant in a way that ensures maximum efficiency during the development and approval process combined with maximum insight in safety and effectiveness of the implant. Even comparative implant testing may become obsolete, which is a big advantage if comparative implant and related data are not available.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This approach to pre-clinical mechanical testing offers the potential to create a chain of arguments, from literature review through testing to the interpretation of test results. This methodology can significantly enhance testing efficiency, reduce risk of failure, and ultimately prevent unnecessary patient suffering and healthcare costs. By synthesizing scientific insights with regulatory requirements, this review aims to guide clinicians and researchers in improving patient care and advancing device technologies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894559","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":"CD24 Positive Nucleus Pulposus Cells in Adult Human Intervertebral Discs Maintain a More Notochordal Phenotype Than GD2 Positive Cells","authors":"Andra-Maria Ionescu,&nbsp;Pauline Baird,&nbsp;Sonal Patel,&nbsp;Gareth Howell,&nbsp;Judith A. Hoyland,&nbsp;Stephen M. Richardson","doi":"10.1002/jsp2.70029","DOIUrl":"10.1002/jsp2.70029","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Notochordal cells (NCs) present in the nucleus pulposus (NP) of the developing human intervertebral disc (IVD) disappear during the first decade of life. This loss coincides with the onset of IVD degeneration, therefore these cells are hypothesized to be important in NP homeostasis. Putative NC-derived (CD24⁺) and progenitor (TIE2⁺/GD2⁺) cell sub-populations have previously been identified in the adult human NP, but their characteristics have yet to be compared. Here, we used CD24, TIE2 and GD2 to identify and then isolate discrete cell sub-populations to assess cell phenotype.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CD24, GD2 and TIE2 positivity was assessed in a cohort of human pediatric and adult NP samples across a range of ages and histological degeneration grades using immunohistochemistry and flow cytometry. FACS sorting was used to isolate different cell sub-populations (CD24⁺/GD2⁺; CD24⁺/GD2⁻; CD24⁻/GD2⁺; CD24⁻/GD2⁻). Cell phenotype was assessed using qPCR for known NC and NP markers as well as catabolic genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CD24⁺ and GD2⁺ cells were localized in all samples, irrespective of age or degeneration grade, while TIE2⁺ cell number was consistently very low. The same positivity trend was confirmed using flow cytometry. A small CD24⁺/GD2⁺ sub-population was present and maintained marker expression with time in culture. CD24⁺ subpopulations showed a significantly higher expression of NC markers than the CD24⁻ subpopulations and unsorted samples, suggesting a healthier phenotype in the CD24⁺ cells. GD2 did not appear to influence gene expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study provides a better understanding of different cell sub-populations present in the adult NP, with identification of CD24⁺/GD2⁺ cells that are maintained with aging and degeneration. Healthy, NC-like phenotypic profiles appeared reliant on CD24, rather than GD2. The study highlights the importance of studying discrete cell sub-populations, especially CD24⁺ NP cells to better understand their role in NP homeostasis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882053","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":"Bone morphogenetic proteins, DNA methylation, and gut microbiota interaction in lumbar disc degeneration: A multi-omics Mendelian randomization study","authors":"Xiang-Yu Li,&nbsp;Peng-Yun Wang,&nbsp;Qi-Jun Wang,&nbsp;Dong-Fan Wang,&nbsp;Shuai-Kang Wang,&nbsp;Yu Wang,&nbsp;Wei-Guo Zhu,&nbsp;Wei Wang,&nbsp;Chao Kong,&nbsp;Shi-Bao Lu,&nbsp;Xiao-Long Chen","doi":"10.1002/jsp2.70027","DOIUrl":"https://doi.org/10.1002/jsp2.70027","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lumbar disc degeneration (LDD) is a ubiquitous finding in low back pain. Many different etiology factors may explain the LDD process, such as bone morphogenetic proteins (BMPs), DNA methylation, and gut microbiota. Until recently the mechanisms underlying the LDD process have been elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>BMP-related genes were extracted from the GeneCards database. The LDD transcriptome dataset was obtained from the Gene Expression Omnibus. We used linear regression and meta-analysis to screen and integrate the differentially expressed genes associated with BMPs in LDD. Genome-wide association studies (GWASs) of LDD were from FinnGen and UKBB. The expression quantitative trait loci (eQTLs) and DNA methylation quantitative trait loci from the blood were identified via the summary data-based Mendelian randomization (SMR) method, and the possible blood BMP genes and their regulatory elements associated with the risk of LDD were prioritized. Intestinal eQTLs and fecal microbial QTLs (mbQTLs) were integrated, and the potential interactions between BMP gene expression in host intestinal tissue and the gut microbiota were revealed through SMR and colocalization analysis. The GWAS catalog (GCST90246169) was used to validate SMR results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A meta-analysis of five datasets revealed that 113 BMP genes were differentially expressed between LDD and control tissues. Seven genes were selected as candidate pathogenic genes of LDD via the three-step SMR method: <i>CREB1</i>, <i>BMP6</i>, <i>PTCH1</i>, <i>GLI1</i>, <i>MEG3</i>, <i>GALNS</i>, and <i>NF1</i>. SMR analysis also revealed five possible gut genes: <i>HFE</i>, <i>MET</i>, <i>MAPK3</i>, <i>NPC1</i>, and <i>GDF5</i>. The correlation between the gut microbiota and BMP gene expression in intestinal tissues was verified by eQTL-mbQTL colocalization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This multi-omics study revealed that the BMP genes associated with LDD are regulated by DNA methylation. There are genetic differences between gut gene expression and the gut microbiota. These findings provide evidence for new therapeutic targets in the future.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"7 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862063","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":"pH: A major player in degenerative intervertebral disks","authors":"Matthew A. R. Trone,&nbsp;Joshua D. Stover,&nbsp;Alejandro Almarza,&nbsp;Robert D. Bowles","doi":"10.1002/jsp2.70025","DOIUrl":"https://doi.org/10.1002/jsp2.70025","url":null,"abstract":"<p>Chronic lower back pain is the leading cause of disability worldwide, generating a socioeconomic cost of over $100 billion annually in the United States. Among the prominent causes of low back pain (LBP) is degeneration of the intervertebral disk (IVD), a condition known as degenerative disk disease (DDD). Despite the prevalence of DDD and multiple studies demonstrating its relationship with LBP, the mechanisms by which it contributes to pain remain unknown. Previous studies have identified potential causes for this pain, such as extracellular matrix (ECM) breakdown, changes in biomechanics, and pro-inflammatory signals. Possible pain treatments targeting these factors have been developed but with limited effects. However, low pH in DDD is a potential pain generator whose role has largely been unexplored and underappreciated. This review highlights hyperacidity's effects on the IVD, such as catabolism of disk cells and ECM, neoinnervation, altered mechanical signaling, and expression of pro-inflammatory cytokines and ion channels. This review aims to discuss what is known about the contributions of acidity to DDD pain, identify the knowledge gaps on this topic, and propose what research can be conducted to fill these gaps. We must better understand the underlying mechanisms of DDD and the interaction between hyperacidity and nociception to develop better therapeutics for this disease.</p>","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/jsp2.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142861802","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":"Scoliosis instrumentation alters primary and coupled motions of the spine: An in vitro study using entire thoracolumbar spine and rib cage specimens","authors":"Christian Liebsch,&nbsp;Peter Obid,&nbsp;Morten Vogt,&nbsp;Benedikt Schlager,&nbsp;Hans-Joachim Wilke","doi":"10.1002/jsp2.70028","DOIUrl":"https://doi.org/10.1002/jsp2.70028","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Effects of rigid posterior instrumentation on the three-dimensional post-operative spinal flexibility are widely unknown. Purpose of this in vitro study was to quantify these effects for characteristic adolescent idiopathic scoliosis instrumentations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Six fresh frozen human thoracic and lumbar spine specimens (C7-S) with entire rib cage from young adult donors (26–45 years) without clinically relevant deformity were loaded quasi-statically with pure moments of 5 Nm in flexion/extension, lateral bending, and axial rotation. Primary and coupled motions of all segments were measured using optical motion tracking. Specimens were tested without instrumentation and with posterior rod instrumentations ranging from T2 to L1 (for Lenke Type 2) and from T8 to L3 (for Lenke Type 5) based on survey results among spinal deformity surgeons. Statistical differences were evaluated using the pairwise Friedman test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Primary ranges of motion were significantly (<i>p</i> &lt; 0.05) reduced in all six motion directions in the entire thoracic spine (T1-L1) for both instrumentations, but solely in extension and axial rotation in the entire lumbar spine (L1-S) for T8-L3 instrumentation. Without instrumentation, strong ipsilateral axial rotation during primary lateral bending and strong contralateral lateral bending during primary axial rotation were detected in the thoracic spine (T1-L1) and slight inverse coupled motions in the lumbar spine (L1-S). While coupled axial rotation was significantly (<i>p</i> &lt; 0.05) reduced, especially in the upper thoracic spine (T1-T5) for T2-L1 instrumentation and in the lumbar spine (L1-S) for T8-L3 instrumentation, coupled lateral bending was solely significantly (<i>p</i> &lt; 0.05) reduced in the upper thoracic spine (T1-T5) for T2-L1 instrumentation. Coupled motions in primary flexion and extension were non-existent and not affected by any fixation (<i>p</i> &gt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Instrumentation reduces the primary flexibility and diminishes the natural coupling behavior between lateral bending and axial rotation, primarily in the upper thoracic spine, potentially causing correction loss and junctional deformity in the long-term.</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/jsp2.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142861803","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":"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}