JOR Spine最新文献_第5页

Intervertebral disc microbiome in Modic changes: Lack of result replication underscores the need for a consensus in low-biomass microbiome analysis 莫迪氏病变中的椎间盘微生物组：缺乏结果复制凸显低生物量微生物组分析需要共识

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-04-04 DOI: 10.1002/jsp2.1330

Tamara Mengis, Natalia Zajac, Laura Bernhard, Irina Heggli, Nick Herger, Jan Devan, Roy Marcus, Florian Brunner, Christoph Laux, Mazda Farshad, Oliver Distler, Stefan Dudli

Introduction

The emerging field of the disc microbiome challenges traditional views of disc sterility, which opens new avenues for novel clinical insights. However, the lack of methodological consensus in disc microbiome studies introduces discrepancies. The aims of this study were to (1) compare the disc microbiome of non-Modic (nonMC), Modic type 1 change (MC1), and MC2 discs to findings from prior disc microbiome studies, and (2) investigate if discrepancies to prior studies can be explained with bioinformatic variations.

Methods

Sequencing of 16S rRNA in 70 discs (24 nonMC, 25 MC1, and 21 MC2) for microbiome profiling. The experimental setup included buffer contamination controls and was performed under aseptic conditions. Methodology and results were contrasted with previous disc microbiome studies. Critical bioinformatic steps that were different in our best-practice approach and previous disc microbiome studies (taxonomic lineage assignment, prevalence cut-off) were varied and their effect on results were compared.

Results

There was limited overlap of results with a previous study on MC disc microbiome. No bacterial genera were shared using the same bioinformatic parameters. Taxonomic lineage assignment using “amplicon sequencing variants” was more sensitive and detected 48 genera compared to 22 with “operational taxonomic units” (previous study). Increasing filter cut-off from 4% to 50% (previous study) reduced genera from 48 to 4 genera. Despite these differences, both studies observed dysbiosis with an increased abundance of gram-negative bacteria in MC discs as well as a lower beta-diversity. Cutibacterium was persistently detected in all groups independent of the bioinformatic approach, emphasizing its prevalence.

Conclusion

There is dysbiosis in MC discs. Bioinformatic parameters impact results yet cannot explain the different findings from this and a previous study. Therefore, discrepancies are likely caused by different sample preparations or true biologic differences. Harmonized protocols are required to advance understanding of the disc microbiome and its clinical implications.

导言：椎间盘微生物组这一新兴领域对椎间盘无菌的传统观点提出了挑战，从而为新的临床见解开辟了新的途径。然而，由于椎间盘微生物组研究的方法缺乏共识，导致研究结果存在差异。本研究的目的是：（1）将非莫迪克（non-MC）、莫迪克 1 型改变（MC1）和 MC2 椎间盘的椎间盘微生物组与之前的椎间盘微生物组研究结果进行比较；（2）研究与之前研究的差异是否可以用生物信息学变化来解释。方法对 70 个圆片（24 个非 MC、25 个 MC1 和 21 个 MC2）中的 16S rRNA 进行测序，以分析微生物组。实验设置包括缓冲液污染控制，并在无菌条件下进行。实验方法和结果与之前的圆盘微生物组研究进行了对比。我们的最佳实践方法与之前的圆盘微生物组研究中不同的关键生物信息学步骤（分类学谱系分配、流行率截断）被改变，并比较了它们对结果的影响。结果与之前关于 MC 盘微生物组的研究结果重叠有限。使用相同的生物信息学参数，没有共享细菌属。使用 "扩增子测序变体 "进行分类系划分的灵敏度更高，检测到 48 个属，而使用 "操作分类单元"（之前的研究）检测到 22 个属。过滤截断率从 4% 提高到 50%（前一项研究），使属从 48 个减少到 4 个。尽管存在这些差异，但这两项研究都观察到了菌群失调现象，即 MC 盘中革兰氏阴性菌的数量增加，β-多样性降低。无论采用哪种生物信息学方法，在所有组别中都能持续检测到切杆菌，强调了切杆菌的普遍性。结论 MC 盘中存在菌群失调。生物信息学参数会影响结果，但无法解释本研究与之前研究的不同结果。因此，差异很可能是由不同的样本制备或真正的生物差异造成的。要加深对椎间盘微生物群及其临床意义的了解，就必须制定统一的方案。

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引用次数: 0

Histological analysis of nucleus pulposus tissue from patients with lumbar disc herniation after condoliase administration 给腰椎间盘突出症患者注射髓核酸酶后髓核组织的组织学分析

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-04-03 DOI: 10.1002/jsp2.1328

Yuka Minamisawa, Taiichi Shirogane, Ippei Watanabe, Akira Dezawa

Background

Condoliase is an enzyme used as a treatment for lumbar disc herniation (LDH). This enzyme degrades chondroitin sulfate (CS) in the nucleus pulposus of the intervertebral disc (IVD). However, there are cases in which symptoms do not improve, despite condoliase administration. This study reports histological analysis of lumbar disc tissue of LDH patients who underwent surgery because condoliase had no therapeutic effect.

Methods

Between March 2019 and August 2019, 12 LDH patients who underwent full endoscopic spine surgery (FESS) discectomy at the Dezawa Akira PED Clinic were the subjects of the study. There are two study groups: six cases underwent FESS after condoliase administration, while six underwent FESS without condoliase administration. The average duration from drug administration to surgery was 152 days. Herniated disc removed at surgery was evaluated by histological staining including immunohistochemistry by anti-CS antibodies.

Results

Multiple large clusters (40–120 μm in diameter) were observed in the nucleus pulposus of those who received condoliase, but no clusters were observed in those who did not. The lumbar disc tissues, including the nucleus pulposus of recipients, were stained with anti-CS antibodies that recognize the CS unsaturated disaccharide, but non-administration tissue was not stained. These findings suggest that the enzyme acted on the nucleus pulposus, even in cases where symptoms were not improved by condoliase administration. Furthermore, there was no histological difference between stained images of the extracellular matrix in those who did or did not receive condoliase, suggesting that condoliase acted specifically on CS in the nucleus pulposus.

Conclusions

We demonstrated that CS in the nucleus pulposus was degraded in patients in whom condoliase did not have a therapeutic effect. Moreover, condoliase acts in human IVD without causing necrosis of chondrocytes and surrounding tissues.

背景 Condoliase 是一种用于治疗腰椎间盘突出症（LDH）的酶。这种酶能降解椎间盘（IVD）髓核中的硫酸软骨素（CS）。然而，在一些病例中，尽管使用了冷凝酶，但症状并没有得到改善。本研究报告了因使用冷凝酶无治疗效果而接受手术治疗的 LDH 患者腰椎间盘组织的组织学分析。方法 2019年3月至2019年8月期间，在出泽明PED诊所接受全内窥镜脊柱手术（FESS）椎间盘切除术的12例LDH患者为研究对象。研究分为两组：6 例患者在使用冷凝酶后接受了 FESS 手术，6 例患者在未使用冷凝酶的情况下接受了 FESS 手术。从用药到手术的平均时间为 152 天。对手术切除的椎间盘进行组织学染色评估，包括抗CS抗体的免疫组化。结果在接受冷凝酶治疗的患者髓核中观察到多个大团（直径 40-120 μm），而未接受冷凝酶治疗的患者髓核中未观察到大团。用识别 CS 不饱和二糖的抗 CS 抗体对腰椎间盘组织（包括接受治疗者的髓核组织）进行染色，但未接受治疗者的组织未被染色。这些研究结果表明，即使在使用髓核酸酶后症状未得到改善的病例中，髓核酸酶也能发挥作用。此外，接受或未接受冷凝酶治疗的患者细胞外基质的染色图像在组织学上没有差异，这表明冷凝酶专门作用于髓核中的CS。结论我们的研究表明，在没有使用冷凝酶治疗的患者中，髓核中的 CS 发生了降解。此外，冷凝酶作用于人类 IVD 不会导致软骨细胞和周围组织坏死。

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引用次数: 0

No evidence of association between either Modic change or disc degeneration and five circulating inflammatory proteins 没有证据表明莫迪氏变化或椎间盘退变与五种循环炎症蛋白之间存在关联

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-03-25 DOI: 10.1002/jsp2.1323

Roger Compte, Maxim B. Freidin, Isabelle Granville Smith, Christine L. Le Maitre, Dovile Vaitkute, Ayrun Nessa, Genevieve Lachance, Frances M. K. Williams

Introduction

Intervertebral disc degeneration and Modic change are the main spinal structural changes associated with chronic low back pain (LBP). Both conditions are thought to manifest local inflammation and if inflammatory proteins translocate to the blood circulation could be detected systemically. The work here assesses whether the presence of disc degeneration is associated with detectable blood level changes of five inflammatory markers and whether chronic LBP is associated with these changes.

Materials and Methods

Two hundred and forty TwinsUK cohort participants with both MRI disc degeneration grade and Modic change extent, and IL-6, IL-8, IL-8 TNF, and CX3CL1 protein blood concentration measurements were included in this work. Linear mixed effects models were used to test the association of blood cytokine concentration with disc degeneration score and Modic change volumetric score. Association of chronic LBP status from questionnaires with disc degeneration, Modic change, and cytokine blood concentration was also tested.

Results

No statistically significant association between disc degeneration or Modic change with cytokine blood concentration was found. Instead, regression analysis pointed strong association between cytokine blood concentration with body mass index for IL-6 and with age for IL-6 and TNF. Mild association was found between IL-8 blood concentration and body mass index. Additionally, LBP status was associated with Modic change volumetric score but not associated with any cytokine concentration.

Conclusions

We found no evidence that Modic change and disc degeneration are able to produce changes in tested blood cytokine concentration. However, age and body mass index have strong influence on cytokine concentration and both are associated with the conditions studied which may confound associations found in the literature. It is then unlikely that cytokines produced in the disc or vertebral bone marrow induce chronic LBP.

导言椎间盘退变和莫迪病变是与慢性腰背痛（LBP）相关的主要脊柱结构变化。这两种情况都被认为表现为局部炎症，如果炎症蛋白转移到血液循环中，则可在全身进行检测。本研究评估了椎间盘退变是否与血液中可检测到的五种炎症标志物的水平变化有关，以及慢性腰背痛是否与这些变化有关。材料和方法 240 名 TwinsUK 队列参与者均进行了 MRI 椎间盘退变等级和 Modic 变化程度以及 IL-6、IL-8、IL-8 TNF 和 CX3CL1 蛋白质血液浓度测量。线性混合效应模型用于检验血液细胞因子浓度与椎间盘退变评分和Modic变化体积评分之间的关系。此外，还测试了通过问卷调查得出的慢性跛行状态与椎间盘退变、Modic变化和细胞因子血液浓度之间的关系。结果没有发现椎间盘退变或 Modic 变化与细胞因子血液浓度之间有统计学意义的关联。相反，回归分析表明，细胞因子血液浓度与 IL-6 的体重指数以及 IL-6 和 TNF 的年龄有密切关系。IL-8的血液浓度与体重指数的关系不大。此外，枸杞多糖状态与莫迪克变化容积评分有关，但与任何细胞因子浓度无关。结论我们没有发现任何证据表明莫迪氏变化和椎间盘退变能够引起血液细胞因子浓度的变化。然而，年龄和体重指数对细胞因子浓度有很大影响，而且两者都与所研究的疾病有关，这可能会混淆文献中发现的关联。因此，椎间盘或脊椎骨骨髓中产生的细胞因子不太可能诱发慢性枸杞痛。

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引用次数: 0

Tracing the disc: The novel qualitative morphometric MRI based disc degeneration classification system 追踪椎间盘：基于磁共振成像的新型椎间盘退变定性形态计量分类系统

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-03-18 DOI: 10.1002/jsp2.1321

Zafer Soydan, Emru Bayramoglu, Devrim Ulas Urut, Ahmet Celal Iplikcioglu, Cengiz Sen

Background

This study aimed to develop a classification system for lumbar disc degeneration using routine magnetic resonance images (MRIs) that is easily applicable and unaffected by existing classifications' limitations, and to compare its reliability, reproducibility, and discriminative power to the widely used Pfirrmann classification.

Methods

Five features were graded. This new classification system has eight grades, with at least one of these five features altering each grade. The T2-weighted sagittal images were acquired using a rapid spin-echo sequence with a repetition time of 2680 to 4900 milliseconds, an echo time of 100 to 109 milliseconds, and an echo train length of 17. Slice thick was 4 mm and the display field of view was 32 × 32 cm. The new classification system used five features: signal intensity, disc height, disc boundary regularity, and nucleus annulus separation. Increased signal intensity, decreased height, decreased regularity, and decreased nucleus-annulus separation indicated degeneration. Four raters classified 400 discs from 80 patients using the Pfirrmann and Novel systems. Statistical analyses were conducted to investigate reliability and correlation.

Results

The overall ICC and kappa values were found to be higher in the novel classification. (0.988 indicating excellent agreement for ICC and 0.76/0.94 indicating good–very good agreement for kappa). The Kendall tau c value, which shows the correlation between the two classifications and indicates the validity of the new classification, was 0.872, which is very strong. Through the use of cross-tabulations, the discriminatory power of the two newly added classification criteria was determined.

Conclusions

This study demonstrates the intra-rater and inter-rater reliability of an easy-to-use, discriminative novel morphometric MRI based classification system for lumbar disc degeneration. The differentiation of grades based on five distinct criteria may generate novel hypotheses regarding treatment selection and response monitoring, as well as new insights into the study of disc degeneration.

背景本研究旨在利用常规磁共振成像（MRI）开发一种腰椎间盘退变分类系统，该系统易于应用且不受现有分类系统局限性的影响，并将其可靠性、可重复性和鉴别力与广泛使用的 Pfirrmann 分类系统进行比较。方法对五个特征进行分级。这一新的分类系统共有八个等级，这五个特征中至少有一个会改变每个等级。T2- 加权矢状面图像采用快速自旋回波序列采集，重复时间为 2680 至 4900 毫秒，回波时间为 100 至 109 毫秒，回波序列长度为 17。切片厚度为 4 毫米，显示视野为 32 × 32 厘米。新的分类系统使用五个特征：信号强度、椎间盘高度、椎间盘边界规则性和髓核环状分离。信号强度增加、高度降低、规则性降低和髓核-髓环分离度降低表示退化。四名评分员使用 Pfirrmann 和 Novel 系统对 80 名患者的 400 个椎间盘进行了分类。对可靠性和相关性进行了统计分析。结果新型分类法的总体 ICC 和 kappa 值更高。(0.988 表示 ICC 的一致性极佳，0.76/0.94 表示 kappa 的一致性良好-非常好）。Kendall tau c 值显示了两种分类之间的相关性，表明新分类的有效性，该值为 0.872，非常高。通过交叉分析，确定了两个新增分类标准的鉴别力。结论本研究证明了基于磁共振成像的腰椎间盘退变分级系统在评分者内部和评分者之间的可靠性。基于五个不同标准的分级可为治疗选择和反应监测提供新的假设，并为椎间盘退变研究提供新的见解。

{"title":"Tracing the disc: The novel qualitative morphometric MRI based disc degeneration classification system","authors":"Zafer Soydan, Emru Bayramoglu, Devrim Ulas Urut, Ahmet Celal Iplikcioglu, Cengiz Sen","doi":"10.1002/jsp2.1321","DOIUrl":"https://doi.org/10.1002/jsp2.1321","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study aimed to develop a classification system for lumbar disc degeneration using routine magnetic resonance images (MRIs) that is easily applicable and unaffected by existing classifications' limitations, and to compare its reliability, reproducibility, and discriminative power to the widely used Pfirrmann classification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Five features were graded. This new classification system has eight grades, with at least one of these five features altering each grade. The T2-weighted sagittal images were acquired using a rapid spin-echo sequence with a repetition time of 2680 to 4900 milliseconds, an echo time of 100 to 109 milliseconds, and an echo train length of 17. Slice thick was 4 mm and the display field of view was 32 × 32 cm. The new classification system used five features: signal intensity, disc height, disc boundary regularity, and nucleus annulus separation. Increased signal intensity, decreased height, decreased regularity, and decreased nucleus-annulus separation indicated degeneration. Four raters classified 400 discs from 80 patients using the Pfirrmann and Novel systems. Statistical analyses were conducted to investigate reliability and correlation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The overall ICC and kappa values were found to be higher in the novel classification. (0.988 indicating excellent agreement for ICC and 0.76/0.94 indicating good–very good agreement for kappa). The Kendall tau <i>c</i> value, which shows the correlation between the two classifications and indicates the validity of the new classification, was 0.872, which is very strong. Through the use of cross-tabulations, the discriminatory power of the two newly added classification criteria was determined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrates the intra-rater and inter-rater reliability of an easy-to-use, discriminative novel morphometric MRI based classification system for lumbar disc degeneration. The differentiation of grades based on five distinct criteria may generate novel hypotheses regarding treatment selection and response monitoring, as well as new insights into the study of disc degeneration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1321","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140145857","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}

引用次数: 0

Intradiscal administration of autologous platelet-rich plasma in patients with Modic type 1 associated low back pain: A prospective pilot study 自体富血小板血浆在莫迪奇 1 型腰痛患者中的椎间盘内给药：前瞻性试点研究

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-03-18 DOI: 10.1002/jsp2.1320

Soya Kawabata, Sota Nagai, Kei Ito, Hiroki Takeda, Daiki Ikeda, Yusuke Kawano, Shinjiro Kaneko, Yukako Shiraishi, Yuichiro Sano, Yoshiharu Ohno, Nobuyuki Fujita

Background

Various treatments for chronic low back pain (LBP) have been reported; among them, platelet-rich plasma (PRP) as a regenerative medicine has attracted much attention. Although Modic type 1 change (MC1) is associated with LBP, no treatment has been established so far. In addition, no studies have administered PRP to intervertebral discs (IVDs) in patients with LBP, targeting MC1 only. Thus, the purpose of this study was to determine the safety and efficacy of PRP administration to the IVDs in patients with MC1 experiencing LBP.

Methods

PRP was injected intradiscally to 10 patients with MC1 experiencing LBP. Patients were followed prospectively for up to 24 weeks after primary administration. Physical condition, laboratory data, and lumbar x-ray images were evaluated for safety assessment. Furthermore, to evaluate the effectiveness of PRP, patient-reported outcomes were considered. In addition, changes in MC1 were assessed using magnetic resonance imaging (MRI).

Results

There were no adverse events in the laboratory data or lumbar X-ray images after administration. The mean visual analog scale, which was 70.0 ± 13.3 before the treatment, significantly decreased 1 week after PRP administration and was 39.0 ± 28.8 at the last observation. Oswestry disability index and Roland Morris disability questionnaire scores promptly improved after treatment, and both improved significantly 24 weeks after PRP administration. Follow-up MRI 24 weeks after treatment showed a significant decrease in the mean high-signal intensity of fat-suppressed T2-weighted imaging from 10.1 to 7.90 mm² compared with that before PRP administration.

Conclusions

The safety and efficacy of PRP administration to the IVDs of patients with MC1 experiencing LBP were identified. Post-treatment MRI suggested improvement in inflammation, speculating that PRP suppressed inflammation and consequently relieved the patient's symptoms. Despite the small number of patients, this treatment is promising for patients with MC1 experiencing LBP. The study protocol has been reviewed and approved by the Certified Committee for Regenerative Medicine and the Japanese Ministry of Health, Labor and Welfare (Japan Registry of Clinical Trials [jRCT] No. jRCTb042210159).

背景已经报道了多种治疗慢性腰背痛（LBP）的方法，其中作为再生医学的富血小板血浆（PRP）备受关注。虽然莫迪奇 1 型改变（MC1）与腰背痛有关，但迄今为止尚未确定治疗方法。此外，也没有任何研究仅针对 MC1 对椎间盘（IVD）注射 PRP。因此，本研究旨在确定对患有 MC1 的椎间盘突出症患者施用 PRP 的安全性和有效性。方法为 10 名腰痛的 MC1 患者在腹腔内注射 PRP。在初次给药后，对患者进行了长达 24 周的前瞻性随访。对患者的身体状况、实验室数据和腰椎 X 光图像进行评估，以进行安全性评估。此外，为了评估 PRP 的有效性，还考虑了患者报告的结果。此外，还使用磁共振成像（MRI）评估了 MC1 的变化。结果用药后，实验室数据和腰椎 X 光图像均未出现不良反应。治疗前的平均视觉模拟量表为（70.0 ± 13.3），注射 PRP 1 周后显著下降，最后一次观察时为（39.0 ± 28.8）。奥斯韦特里残疾指数和罗兰-莫里斯残疾问卷评分在治疗后迅速改善，在注射 PRP 24 周后均有明显改善。治疗 24 周后的磁共振成像随访显示，与使用 PRP 前相比，脂肪抑制 T2 加权成像的平均高信号强度从 10.1 mm2 显著降至 7.90 mm2。结论对腰椎间盘突出症 MC1 患者的 IVD 施用 PRP 具有安全性和有效性。治疗后的磁共振成像显示炎症有所改善，推测 PRP 抑制了炎症，从而缓解了患者的症状。尽管患者人数较少，但这种治疗方法对于患有枸杞多糖症的 MC1 患者来说前景广阔。该研究方案已通过再生医学认证委员会和日本厚生劳动省的审查和批准（日本临床试验登记[jRCT]编号：jRCTb042210159）。

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引用次数: 0

Correction to ‘Recommendations for intervertebral disc notochordal cell investigation: From isolation to characterization’ 对 "椎间盘脊索间细胞调查建议 "的更正：从分离到定性

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-03-04 DOI: 10.1002/jsp2.1317

Williams RJ, Laagland LT, Bach FC, Ward L, Chan W, Tam V, Medzikovic A, Basatvat S, Paillat L, Vedrenne N, Snuggs JW, Poramba-Liyanage DW, Hoyland JA, Chan D, Camus A, Richardson SM, Tryfonidou MA, Le Maitre CL. Recommendations for intervertebral disc notochordal cell investigation: From isolation to characterization. JOR Spine 2023;6:e1272. doi: 10.1002/jsp2.1272

The article cited above omitted an ethical review statement regarding access to human fetal samples used as examples within Figure 2 and prior development of the extractions methodology as recommended:

Ethics Statement

Fetal samples utilised in this study were obtained from full informed consent following medical or surgical pregnancy termination and were approved by the National Research Ethics Committee (UK) (Fetal approval number: 13/NW/0205, Paediatric approval number: 12/NW/0437).

In addition, there was a minor error in the Author Contributions; the correct text is shown below.

Rebecca J. Williams, Lisanne T. Laagland, Frances C. Bach, Lizzy Ward, Shaghayegh Basatvat, Wilson Chan, Joseph W. Snuggs, and Lily Paillat contributed to acquisition of laboratory data (Rebecca J. Williams: Porcine and Rat isolation, numeration studies, characterization, and culture; Lisanne T. Laagland: Canine and porcine isolation and characterization; Frances C. Bach: canine, and porcine isolation; Lizzy Ward: human isolation; Shaghayegh Basatvat: porcine isolation; Wilson Chan: mouse isolation; Joseph W. Snuggs: rat isolation, monolayer culture, and characterization; Lily Paillat: mouse isolation).

We apologize for this error.

Williams RJ、Laagland LT、Bach FC、Ward L、Chan W、Tam V、Medzikovic A、Basatvat S、Paillat L、Vedrenne N、Snuggs JW、Poramba-Liyanage DW、Hoyland JA、Chan D、Camus A、Richardson SM、Tryfonidou MA、Le Maitre CL。椎间盘脊索间细胞研究建议：从分离到表征。JOR Spine 2023;6:e1272. doi: 10.1002/jsp2.1272上述文章遗漏了有关获取图 2 中用作示例的人类胎儿样本的伦理审查声明，以及事先开发提取方法的建议：伦理声明本研究中使用的胎儿样本是在医疗或手术终止妊娠后经完全知情同意获得的，并已获得英国国家研究伦理委员会批准（胎儿批准号：13/NW/0205，儿科批准号：12/NW/0437）。Rebecca J. Williams、Lisanne T. Laagland、Frances C. Bach、Lizzy Ward、Shaghayegh Basatvat、Wilson Chan、Joseph W. Snuggs 和 Lily Paillat 对实验室数据的采集做出了贡献（Rebecca J. Williams：猪和大鼠的分离、编号研究、特征描述和培养；Lisanne T. Laagland：Frances C. Bach：犬和猪分离；Lizzy Ward：人类分离；Shaghayegh Basatvat：猪分离；Wilson Chan：小鼠分离；Joseph W. Snuggs：大鼠分离、单层培养和特征描述；Lily Paillat：小鼠分离。

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引用次数: 0

Comparative analysis of paraspinal muscle imbalance between idiopathic scoliosis and congenital scoliosis from the transcriptome aspect 从转录组角度比较分析特发性脊柱侧弯症和先天性脊柱侧弯症的脊柱旁肌肉失衡问题

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-03-04 DOI: 10.1002/jsp2.1318

Zhen Wang, Junduo Zhao, Haining Tan, Yang Jiao, Xin Chen, Jianxiong Shen

Background

Previous studies have analyzed paraspinal muscle imbalance in idiopathic scoliosis (IS) with methods including imaging, histology and electromyography. However, whether paraspinal muscle imbalance is the cause or the consequence of spinal deformities in IS remains unclear. Comparison of paraspinal muscle imbalance between IS and congenital scoliosis (CS) may shed some light on the causality of paraspinal muscle imbalance and IS. This study aimed to elucidate the generality and individuality of paraspinal muscle imbalance between IS and CS from gene expression.

Methods

Five pairs of surgical-treated IS and CS patients were matched. Bilateral paraspinal muscles at the apex were collected for transcriptome sequencing. Differentially expressed genes (DEGs) between the convexity and concavity in both IS and CS were identified. Comparison of DEGs between IS and CS was conducted to discriminate IS-specific DEGs from DEGs shared by both IS and CS. Bioinformatics analysis was performed. The top 10 hub genes in the protein–protein interaction (PPI) network of IS-specific DEGs were validated by quantitative PCR (qPCR) in 10 pairs of IS and CS patients.

Results

A total of 370 DEGs were identified in IS, whereas 380 DEGs were identified in CS. Comparison of DEGs between IS and CS identified 59 DEGs shared by IS and CS, along with 311 DEGs specific for IS. These IS-specific DEGs were enriched in response to external stimulus and signaling receptor binding in GO terms and calcium signaling pathway in KEGG pathways. The top 10 hub genes in the PPI network of IS-specific DEGs include BDKRB1, PRH1-TAS2R14, CNR2, NPY4R, HTR1E, CXCL3, ICAM1, ALB, ADIPOQ, and GCGR. Among these hub genes, the asymmetrical expression of PRH1-TAS2R14 and ADIPOQ in IS but not CS were validated by qPCR.

Conclusions

Transcriptomic differences in bilateral paraspinal muscles between the convexity and concavity in IS share few similarities with those in CS.

背景以往的研究通过影像学、组织学和肌电图等方法分析了特发性脊柱侧弯症（IS）的脊柱旁肌肉失衡。然而，脊柱旁肌肉失衡是导致特发性脊柱侧弯症脊柱畸形的原因还是结果仍不清楚。比较IS和先天性脊柱侧弯症（CS）的脊柱旁肌肉失衡可能会对脊柱旁肌肉失衡和IS的因果关系有所启发。本研究旨在从基因表达的角度阐明IS和CS脊柱旁肌肉失衡的普遍性和个体性。方法对五对经过手术治疗的 IS 和 CS 患者进行配对。采集双侧脊柱旁顶点肌肉进行转录组测序。确定了IS和CS凸面和凹面之间的差异表达基因（DEGs）。对 IS 和 CS 的 DEGs 进行比较，以区分 IS 特异的 DEGs 和 IS 与 CS 共享的 DEGs。进行了生物信息学分析。在10对IS和CS患者中通过定量PCR（qPCR）验证了IS特异性DEGs的蛋白-蛋白相互作用（PPI）网络中的前10个枢纽基因。结果在 IS 中发现了 370 个 DEGs，而在 CS 中发现了 380 个 DEGs。通过比较 IS 和 CS 的 DEGs，发现 IS 和 CS 共有 59 个 DEGs，IS 特异的 DEGs 有 311 个。这些IS特异的DEGs在GO术语中富集于对外部刺激的反应和信号受体结合，在KEGG通路中富集于钙信号通路。在 IS 特异性 DEGs 的 PPI 网络中，前 10 个枢纽基因包括 BDKRB1、PRH1-TAS2R14、CNR2、NPY4R、HTR1E、CXCL3、ICAM1、ALB、ADIPOQ 和 GCGR。在这些枢纽基因中，通过 qPCR 验证了 PRH1-TAS2R14 和 ADIPOQ 在 IS 中的非对称表达，而在 CS 中则没有。结论 IS 双侧脊柱旁肌肉凸面和凹面的转录组差异与 CS 几乎没有相似之处。

{"title":"Comparative analysis of paraspinal muscle imbalance between idiopathic scoliosis and congenital scoliosis from the transcriptome aspect","authors":"Zhen Wang, Junduo Zhao, Haining Tan, Yang Jiao, Xin Chen, Jianxiong Shen","doi":"10.1002/jsp2.1318","DOIUrl":"https://doi.org/10.1002/jsp2.1318","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Previous studies have analyzed paraspinal muscle imbalance in idiopathic scoliosis (IS) with methods including imaging, histology and electromyography. However, whether paraspinal muscle imbalance is the cause or the consequence of spinal deformities in IS remains unclear. Comparison of paraspinal muscle imbalance between IS and congenital scoliosis (CS) may shed some light on the causality of paraspinal muscle imbalance and IS. This study aimed to elucidate the generality and individuality of paraspinal muscle imbalance between IS and CS from gene expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Five pairs of surgical-treated IS and CS patients were matched. Bilateral paraspinal muscles at the apex were collected for transcriptome sequencing. Differentially expressed genes (DEGs) between the convexity and concavity in both IS and CS were identified. Comparison of DEGs between IS and CS was conducted to discriminate IS-specific DEGs from DEGs shared by both IS and CS. Bioinformatics analysis was performed. The top 10 hub genes in the protein–protein interaction (PPI) network of IS-specific DEGs were validated by quantitative PCR (qPCR) in 10 pairs of IS and CS patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 370 DEGs were identified in IS, whereas 380 DEGs were identified in CS. Comparison of DEGs between IS and CS identified 59 DEGs shared by IS and CS, along with 311 DEGs specific for IS. These IS-specific DEGs were enriched in response to external stimulus and signaling receptor binding in GO terms and calcium signaling pathway in KEGG pathways. The top 10 hub genes in the PPI network of IS-specific DEGs include <i>BDKRB1</i>, <i>PRH1-TAS2R14</i>, <i>CNR2</i>, <i>NPY4R</i>, <i>HTR1E</i>, <i>CXCL3</i>, <i>ICAM1</i>, <i>ALB</i>, <i>ADIPOQ</i>, and <i>GCGR</i>. Among these hub genes, the asymmetrical expression of <i>PRH1-TAS2R14</i> and <i>ADIPOQ</i> in IS but not CS were validated by qPCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Transcriptomic differences in bilateral paraspinal muscles between the convexity and concavity in IS share few similarities with those in CS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.1318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140024742","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}

引用次数: 0

Evaluating the causal effect of atherosclerosis on the risk of intervertebral disc degeneration 评估动脉粥样硬化对椎间盘退化风险的因果影响

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-03-04 DOI: 10.1002/jsp2.1319

Yang-Ting Cai, Xian-Xing Zhong, Ling Mo, Rui-Ze Huang, Qiang Lin, Cai-Jun Liu, Shun-Cong Zhang

Background

Intervertebral disc degeneration (IDD) and atherosclerosis are two common age-related conditions that can cause significant morbidity. While previous studies have suggested an association between the two conditions, the nature of this association remains unclear.

Methods

We used Mendelian randomization (MR) to investigate the causal relationship between IDD and atherosclerosis. We identified genetic variants associated with IDD using summary statistics from a large genome-wide association study (GWAS). These variants were then used as instrumental variables to infer causal relationships with atherosclerosis in summary statistics from a separate GWAS.

Results

Our MR analysis provided evidence for a causal relationship between IDD and atherosclerosis. We found that the genetic predisposition to atherosclerosis was associated with a higher risk of IDD (odds ratio [OR] = 3.55, 95% confidence interval [CI]: 1.07–11.74, p = 0.04). The IVW estimates were consistent with the observational findings and other robust MR methods. Sensitivity analyses suggested that our findings were robust to potential sources of bias.

Conclusions

Our study provides evidence for a causal link between IDD and atherosclerosis, suggesting that interventions targeting atherosclerosis could have potential benefits for reducing the risk of IDD. Further research is needed to explore the underlying mechanisms that link these two conditions and to investigate potential therapeutic interventions.

背景椎间盘退变（IDD）和动脉粥样硬化是两种常见的与年龄有关的疾病，可导致严重的发病率。虽然以前的研究表明这两种疾病之间存在关联，但这种关联的性质仍不清楚。方法我们采用孟德尔随机法（MR）研究 IDD 和动脉粥样硬化之间的因果关系。我们利用大型全基因组关联研究（GWAS）的汇总统计数据确定了与 IDD 相关的遗传变异。然后将这些变异作为工具变量，从另一项全基因组关联研究的汇总统计中推断与动脉粥样硬化的因果关系。结果我们的磁共振分析为 IDD 与动脉粥样硬化之间的因果关系提供了证据。我们发现，动脉粥样硬化的遗传易感性与较高的 IDD 风险相关（比值比 [OR] = 3.55，95% 置信区间 [CI]：1.07-11.74，p = 0.04）。IVW估计值与观察结果和其他稳健的磁共振方法一致。敏感性分析表明，我们的研究结果对潜在的偏倚来源是稳健的。结论我们的研究为 IDD 与动脉粥样硬化之间的因果关系提供了证据，表明针对动脉粥样硬化的干预措施可能对降低 IDD 风险有益。还需要进一步的研究来探索将这两种疾病联系在一起的潜在机制，并调查潜在的治疗干预措施。

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引用次数: 0

The role of the complement system in disc degeneration and Modic changes 补体系统在椎间盘退变和莫迪变化中的作用

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-02-02 DOI: 10.1002/jsp2.1312

Irina Heggli, Graciosa Q. Teixeira, James C. Iatridis, Cornelia Neidlinger-Wilke, Stefan Dudli

Disc degeneration and vertebral endplate bone marrow lesions called Modic changes are prevalent spinal pathologies found in chronic low back pain patients. Their pathomechanisms are complex and not fully understood. Recent studies have revealed that complement system proteins and interactors are dysregulated in disc degeneration and Modic changes. The complement system is part of the innate immune system and plays a critical role in tissue homeostasis. However, its dysregulation has also been associated with various pathological conditions such as rheumatoid arthritis and osteoarthritis. Here, we review the evidence for the involvement of the complement system in intervertebral disc degeneration and Modic changes. We found that only a handful of studies reported on complement factors in Modic changes and disc degeneration. Therefore, the level of evidence for the involvement of the complement system is currently low. Nevertheless, the complement system is tightly intertwined with processes known to occur during disc degeneration and Modic changes, such as increased cell death, autoantibody production, bacterial defense processes, neutrophil activation, and osteoclast formation, indicating a contribution of the complement system to these spinal pathologies. Based on these mechanisms, we propose a model how the complement system could contribute to the vicious cycle of tissue damage and chronic inflammation in disc degeneration and Modic changes. With this review, we aim to highlight a currently understudied but potentially important inflammatory pathomechanism of disc degeneration and Modic changes that may be a novel therapeutic target.

椎间盘退变和椎体终板骨髓病变（称为莫迪克病变）是慢性腰背痛患者普遍存在的脊柱病变。其病理机制复杂，尚未完全明了。最近的研究发现，在椎间盘变性和 Modic 病变中，补体系统蛋白和相互作用因子失调。补体系统是先天性免疫系统的一部分，在组织稳态中发挥着关键作用。然而，它的失调也与类风湿性关节炎和骨关节炎等多种病症有关。在此，我们回顾了补体系统参与椎间盘退变和莫迪变化的证据。我们发现，只有少数研究报告了莫迪奇变化和椎间盘退变中的补体因素。因此，目前关于补体系统参与的证据水平还很低。然而，补体系统与已知的椎间盘退变和莫迪氏病变过程密切相关，如细胞死亡增加、自身抗体产生、细菌防御过程、中性粒细胞活化和破骨细胞形成等，这表明补体系统对这些脊柱病变有一定的作用。基于这些机制，我们提出了一个模型，说明补体系统如何在椎间盘退变和 Modic 病变中促成组织损伤和慢性炎症的恶性循环。通过这篇综述，我们旨在强调椎间盘退变和莫迪氏病变的一个目前未被充分研究但却具有潜在重要性的炎症病理机制，它可能成为一个新的治疗靶点。

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引用次数: 0

Integrated DNA methylation analysis reveals a potential role for PTPRN2 in Marfan syndrome scoliosis DNA 甲基化综合分析揭示了 PTPRN2 在马凡氏综合征脊柱侧凸中的潜在作用。

IF 3.7 3区医学 Q1 Medicine

JOR Spine

Pub Date : 2024-01-29 DOI: 10.1002/jsp2.1304

Zhen-zhong Zheng, Jing-hong Xu, Jia-lin Chen, Bin Jiang, Hong Ma, Lei Li, Ya-wei Li, Yu-liang Dai, Bing Wang

Background

Marfan syndrome (MFS) is a rare genetic disorder caused by mutations in the Fibrillin-1 gene (FBN1) with significant clinical features in the skeletal, cardiopulmonary, and ocular systems. To gain deeper insights into the contribution of epigenetics in the variability of phenotypes observed in MFS, we undertook the first analysis of integrating DNA methylation and gene expression profiles in whole blood from MFS and healthy controls (HCs).

Methods

The Illumina 850K (EPIC) DNA methylation array was used to detect DNA methylation changes on peripheral blood samples of seven patients with MFS and five HCs. Associations between methylation levels and clinical features of MFS were analyzed. Subsequently, we conducted an integrated analysis of the outcomes of the transcriptome data to analyze the correlation between differentially methylated positions (DMPs) and differentially expressed genes (DEGs) and explore the potential role of methylation-regulated DEGs (MeDEGs) in MFS scoliosis. The weighted gene co-expression network analysis was used to find gene modules with the highest correlation coefficient with target MeDEGs to annotate their functions in MFS.

Results

Our study identified 1253 DMPs annotated to 236 genes that were primarily associated with scoliosis, cardiomyopathy, and vital capacity. These conditions are typically associated with reduced lifespan in untreated MFS. We calculated correlations between DMPs and clinical features, such as cobb angle to evaluate scoliosis and FEV1% to assess pulmonary function. Notably, cg20223687 (PTPRN2) exhibited a positive correlation with cobb angle of scoliosis, potentially playing a role in ERKs inactivation.

Conclusions

Taken together, our systems-level approach sheds light on the contribution of epigenetics to MFS and offers a plausible explanation for the complex phenotypes that are linked to reduced lifespan in untreated MFS patients.

背景：马凡综合征（MFS）是由纤连蛋白-1基因（FBN1）突变引起的一种罕见遗传性疾病，在骨骼、心肺和眼部系统具有显著的临床特征。为了深入了解表观遗传学在 MFS 表型变异中的作用，我们首次对 MFS 和健康对照组（HCs）全血的 DNA 甲基化和基因表达谱进行了整合分析：方法：使用Illumina 850K (EPIC) DNA甲基化阵列检测7名MFS患者和5名健康对照者外周血样本的DNA甲基化变化。分析了甲基化水平与 MFS 临床特征之间的关联。随后，我们对转录组数据的结果进行了综合分析，分析了差异甲基化位点（DMPs）与差异表达基因（DEGs）之间的相关性，并探讨了甲基化调控的DEGs（MeDEGs）在MFS脊柱侧凸中的潜在作用。通过加权基因共表达网络分析，找到与目标 MeDEGs 相关系数最高的基因模块，以注释它们在 MFS 中的功能：我们的研究发现了1253个DMPs，注释了236个基因，这些基因主要与脊柱侧弯、心肌病和生命能力有关。这些情况通常与未经治疗的 MFS 的寿命缩短有关。我们计算了 DMP 与临床特征之间的相关性，如评估脊柱侧弯的 cobb 角和评估肺功能的 FEV1%。值得注意的是，cg20223687（PTPRN2）与脊柱侧弯的柯布角呈正相关，可能在ERKs失活中发挥作用：综上所述，我们的系统水平方法揭示了表观遗传学对 MFS 的贡献，并为 MFS 患者未经治疗而寿命缩短的复杂表型提供了合理的解释。

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引用次数: 0