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In Vivo Measurements Reveal Increased Nucleus Pulposus Lactate and Oxygen Concentrations in a Goat Model of Intervertebral Disc Degeneration 在体内测量显示增加髓核乳酸和氧浓度在山羊椎间盘退变模型
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-05-27 DOI: 10.1002/jsp2.70076
Karthikeyan Rajagopal, Thomas P. Schaer, Kyle D. Meadows, Madeline Boyes, Rachel Hilliard, John C. O'Donnell, George R. Dodge, Dmitriy Petrov, Dawn M. Elliott, Robert L. Mauck, Lachlan J. Smith, Neil R. Malhotra

Introduction

Intervertebral disc degeneration is strongly implicated as a cause of low back pain. Although the precise pathophysiological mechanisms remain elusive, perturbations in nutrition that adversely impact the cellular microenvironment of the central nucleus pulposus (NP) may be contributing factors. A comprehensive understanding of this microenvironment, including changes in nutrient availability as a function of degeneration, is critical for the development of effective cell-based treatments. The goal of this study was to adapt brain tissue oxygen probes and microdialysis catheters for in situ determination of relative NP oxygen, glucose, and lactate levels in a preclinical goat model of disc degeneration.

Methods

Following ex vivo technical refinement in bovine caudal discs, baseline metabolite measurements were performed in vivo in the lumbar discs of 3 large frame goats. Degeneration was then induced via injection of chondroitinase ABC (ChABC) into the NP, and measurements were repeated after 12 weeks. Degeneration severity was graded using magnetic resonance imaging (MRI) and histology, and vertebral endplate porosity was assessed using microcomputed tomography.

Results

Oxygen and lactate levels in goat NPs were significantly higher in degenerate compared to healthy discs, while glucose levels were not significantly different. ChABC-injected discs exhibited higher vertebral endplate porosity, worse histological and MRI grades, and a spectrum of cartilage endplate damage compared to healthy discs. There were significant positive correlations between MRI grade and both NP oxygen and lactate levels.

Discussion

We successfully adapted techniques including surgical placement, equilibration time, flow rate, and detection method for in situ measurement of oxygen, glucose, and lactate in a goat model of disc degeneration. Interestingly, while increased lactate with degeneration was expected, increased oxygen levels were unexpected. Our findings may, in part, be explained by associated alterations in disc and endplate structure, and motivate future studies to comprehensively establish the underlying mechanisms in this model.

椎间盘退变是腰痛的一个重要原因。虽然确切的病理生理机制尚不清楚,但对中央髓核(NP)细胞微环境产生不利影响的营养扰动可能是促成因素。全面了解这种微环境,包括作为退化功能的营养可用性的变化,对于开发有效的细胞治疗至关重要。本研究的目的是采用脑组织氧探针和微透析导管原位测定临床前山羊椎间盘退变模型的相对NP氧、葡萄糖和乳酸水平。方法在牛尾椎间盘的离体技术改进后,对3只大型山羊的腰椎间盘进行了基线代谢物的体内测量。然后通过向NP中注射软骨素酶ABC (ChABC)诱导变性,并在12周后重复测量。使用磁共振成像(MRI)和组织学对退变严重程度进行分级,使用显微计算机断层扫描评估椎体终板孔隙度。结果山羊变性椎间盘内氧和乳酸水平显著高于正常椎间盘,而葡萄糖水平无显著差异。与健康椎间盘相比,注射chabc的椎间盘表现出更高的椎体终板孔隙度,更差的组织学和MRI分级,以及软骨终板损伤谱。MRI分级与NP氧和乳酸水平呈正相关。在山羊椎间盘退变模型中,我们成功地采用了包括手术位置、平衡时间、流速和原位测量氧、葡萄糖和乳酸的检测方法在内的技术。有趣的是,虽然乳酸水平升高与变性是意料之中的,但氧水平升高是意料之外的。我们的发现可以部分解释为椎间盘和终板结构的相关改变,并激励未来的研究全面建立该模型的潜在机制。
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引用次数: 0
In Vitro Validation of Pulsed Electromagnetic Field (PEMF) as an Effective Countermeasure Against Inflammatory-Mediated Intervertebral Disc Degeneration 脉冲电磁场(PEMF)作为炎症介导的椎间盘退变有效对策的体外验证
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-05-19 DOI: 10.1002/jsp2.70077
Laura Guarnaccia, Laura Begani, Silvana Pileggi, Mauro Pluderi, Stefano Borsa, Claudia Fanizzi, Massimiliano Domenico Rizzaro, Giorgio Fiore, Laura Fontana, Rolando Campanella, Chiara Cordiglieri, Chiara Gaudino, Giovanni A. Alotta, Monica Miozzo, Emanuele Garzia, Emanuela Barilla, Lorenzo Fassina, Laura Riboni, Marco Locatelli, Giovanni Marfia, Stefania E. Navone

Background

Intervertebral disc (IVD) degeneration (IDD) is the main contributor to chronic low back pain (LBP), the leading cause of disability worldwide, with a significant impact on the quality of life and health of common people. The etiology of IDD is still unclear, but it has been largely demonstrated the crucial role of inflammation and neuroinflammation in the pathological and degenerative cascade of events characterizing IVD degeneration.

Aim

In this study, we evaluated the potential therapeutic effect of pulsed electromagnetic field (PEMF) on human degenerated IVD (D-IVD) cells collected from patients who underwent discectomy.

Materials & Methods

The experimental plan to test our hypothesis, involved viability assay, reactive oxide species/nitrite production, gene, and protein expression. To recapitulate the pro-inflammatory disc microenvironment occurring during IDD, interleukin-1β (IL-1β) was administered to IVD cell culture. Then, to dissect the contribution of neuroinflammatory condition to immune component, microglial cells were co-cultured with IVD-conditioned media, and viability and expression of inflammatory markers were detected.

Results

Our data prove that in the IVD degenerative microenvironment, the increase of pro-inflammatory mediators, extracellular matrix degradative enzymes, and neuroinflammatory markers could be reduced by PEMF therapy, resulting in an overall improvement of degenerative condition and LBP.

Conclusion

These results represent an impactful novelty for the management of people suffering from LPB, in terms of symptom relief and reduction of social-health system burden.

背景椎间盘退变(IDD)是导致慢性腰痛(LBP)的主要原因,是全球致残的主要原因,对普通人的生活质量和健康产生重大影响。IDD的病因尚不清楚,但已经在很大程度上证明了炎症和神经炎症在IVD变性的病理和退行性级联事件中的关键作用。目的在本研究中,我们评估脉冲电磁场(PEMF)对椎间盘切除术患者退行性IVD (D-IVD)细胞的潜在治疗效果。材料,方法采用活力测定、活性氧化物/亚硝酸盐生成、基因和蛋白表达等实验方法来验证我们的假设。为了重现IDD期间发生的促炎性椎间盘微环境,我们将白细胞介素-1β (IL-1β)注射到IVD细胞培养中。然后,为了解剖神经炎症对免疫成分的贡献,将小胶质细胞与ivd条件培养基共培养,检测炎症标志物的活力和表达。结果我们的数据证明,在IVD退行性微环境中,PEMF治疗可以减少促炎介质、细胞外基质降解酶和神经炎症标志物的增加,从而导致退行性疾病和LBP的整体改善。结论从症状缓解和减轻社会卫生系统负担的角度来看,这些结果为LPB患者的管理提供了一个有影响力的新颖性。
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引用次数: 0
TNFα Receptor 1 and Not Receptor 2 Affect Annulus Fibrosus and Nucleus Pulposus Response to Cytokine Challenge in a Rat Model TNFα受体1和非受体2影响大鼠纤维环和髓核对细胞因子刺激的反应
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-05-19 DOI: 10.1002/jsp2.70070
Timothy D. Jacobsen, S. Olga Yiantsos, Jennifer Gansau, James Meyers, Damien Laudier, James C. Iatridis

Background

Painful intervertebral disc (IVD) degeneration (IVDD) involves chronic inflammation. Developing translational immunomodulatory strategies for IVDD is a priority with tumor necrosis factor alpha (TNFα) signaling an important target. TNFα binds to 2 receptors (TNFRs), with TNFR1 signaling promoting catabolism and apoptosis and TNFR2 signaling promoting anabolism and proliferation.

Methods

This study developed translational strategies to evaluate and modulate TNFR1 and TNFR2 signaling in rat in vivo and in vitro IVDD models. We used blocking antibodies, the TNFR2-activator Atsttrin, and small molecule inhibitors of TNFR1 to discern distinct TNFR1 and TNFR2-effects on annulus fibrosus (AF) and nucleus pulposus (NP) cells and to identify effective strategies for modulating specific TNFRs.

Results

TNFR1 was significantly increased with IVDD in vivo in the NP while TNFR2 was unaffected with very faint staining. TNFR1-specific small molecule inhibitors were effective in reducing catabolic effects of TNFα, highlighting the efficacy of this small molecule strategy for TNFR1 signaling modulation. Meanwhile, TNFR1 and TNFR2 inhibition in vitro was not effective with blocking antibodies on NP or AF cells, likely due to species-specificity of available blocking antibodies. Further, TNFR2 activation with Atsttrin was similarly ineffective, likely due to extremely low TNFR2 levels in both AF and NP cells.

Conclusions

TNFα receptor-specific signaling is important in rat IVDD in vivo and in vitro. TNFR1 inhibition was more effective with small molecules than using blocking antibodies. Low levels of TNFR2 in rat AF and NP cells and lack of efficacy of TNFR2-activator Atsttrin suggest native AF and NP cells have little capacity for TNFR2-dependent IVD repair.

疼痛性椎间盘退变(IVD)涉及慢性炎症。以肿瘤坏死因子α (TNFα)信号为重要靶点,开发IVDD的翻译免疫调节策略是当务之急。TNFα结合2受体(TNFRs),其中TNFR1信号促进分解代谢和细胞凋亡,TNFR2信号促进合成代谢和细胞增殖。方法本研究在大鼠体内和体外IVDD模型中制定了评估和调节TNFR1和TNFR2信号通路的翻译策略。我们使用阻断抗体、tnfr2激活剂atstrin和TNFR1的小分子抑制剂来辨别TNFR1和tnfr2对纤维环(AF)和髓核(NP)细胞的不同作用,并确定调节特异性TNFRs的有效策略。结果IVDD显著提高了NP组织TNFR1的活性,TNFR2染色微弱,未受影响。TNFR1特异性小分子抑制剂可有效降低tnf - α的分解代谢作用,突出了这种小分子策略对TNFR1信号调节的功效。同时,TNFR1和TNFR2的体外抑制对NP或AF细胞的阻断抗体无效,可能是由于可用的阻断抗体的物种特异性。此外,atstrin对TNFR2的激活同样无效,可能是由于AF和NP细胞中TNFR2水平极低。结论TNFα受体特异性信号在体内外大鼠IVDD中起重要作用。小分子抑制TNFR1比阻断抗体更有效。大鼠AF和NP细胞中TNFR2水平低,且缺乏TNFR2激活剂atstrin的效力,表明天然AF和NP细胞缺乏TNFR2依赖性IVD修复能力。
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引用次数: 0
An Extracellular Matrix Hydrogel Restores Disc Volume and Alleviates Axial Hypersensitivity in a Rat Model of Disc-Associated Pain 细胞外基质水凝胶在大鼠椎间盘相关疼痛模型中恢复椎间盘体积并减轻轴向超敏反应
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-05-15 DOI: 10.1002/jsp2.70073
David J. Lillyman, Evie C. Reddick, Kayla E. Ney, Sydney M. Caparaso, Rebecca A. Wachs

Background

Chronic low back pain is a global socioeconomic crisis, and the majority of those treated for this condition fail to reach long-term remission. Intervertebral disc degeneration is the predominant associative factor in chronic low back pain. Degenerated discs present with mechanical instability, inflammation, and nerve sprouting. Patients treated with spinal stabilizing procedures often report pain alleviation indicating aberrant spinal mechanics, could be causative in the production of pain.

Methods

With this knowledge, a therapeutic was engineered from decellularized healthy porcine nucleus pulposus tissue mixed with type I collagen and a chemical crosslinker, genipin, to treat mechanical instability and pain.

Results

In vitro, this hydrogel, termed dNP+, was spontaneously fibrillogenic at 37°C and cytocompatible with primary human disc cells and exhibited the capacity to improve the intervertebral disc storage modulus after injury. In vivo, in a rat model of discogenic low back pain, dNP+ proved effective at restoring degenerated disc volume, decreasing axial hypersensitivity, and decreasing spontaneous pain-like behavior when administered 9 weeks after disc degeneration was initiated. However, dNP+ did not alter nerve presence or restore disc morphology when compared to injured discs.

Conclusion

Conclusion: Altogether, the data collected in this study concluded that dNP+ was an effective treatment for pain-like behavior in a robust animal model of chronic disc-associated low back pain.

慢性腰痛是一种全球性的社会经济危机,大多数接受治疗的患者未能达到长期缓解。椎间盘退变是慢性腰痛的主要相关因素。椎间盘退变表现为机械不稳定、炎症和神经萌芽。接受脊柱稳定手术治疗的患者经常报告疼痛减轻,这表明脊柱力学异常,可能是疼痛产生的原因。方法利用脱细胞的健康猪髓核组织,与I型胶原蛋白和化学交联剂genipin混合,设计一种治疗机械不稳定和疼痛的药物。结果在体外,该水凝胶(dNP+)在37°C下自发成纤维,与人原代椎间盘细胞细胞相容,并表现出提高损伤后椎间盘储存模量的能力。在体内,在椎间盘源性腰痛的大鼠模型中,dNP+在椎间盘退变开始9周后被证明可以有效地恢复退变的椎间盘体积,减少轴向超敏反应,减少自发的疼痛样行为。然而,与受损椎间盘相比,dNP+并没有改变神经存在或恢复椎间盘形态。结论:总之,本研究收集的数据表明,dNP+在稳健的慢性椎间盘相关性腰痛动物模型中是一种有效的疼痛样行为治疗方法。
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引用次数: 0
The Role of Sex Hormones in Cartilaginous Tissues: A Scoping Review 性激素在软骨组织中的作用:综述
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-05-15 DOI: 10.1002/jsp2.70072
Jeffrey L. Hutchinson, Amalie J. Hutchinson, Joy Feng, Cheryle A. Séguin

Background

The use of sex hormones in the clinic for the management of musculoskeletal conditions is increasingly common. Despite this, the role of sex hormones in various joint tissues such as the intervertebral disc (IVD), temporomandibular joint (TMJ), and articular cartilage remains poorly understood. Here, we employ a database search strategy to critically examine the available literature in this field through a scoping review.

Methods

Using a 4-step protocol, primary research articles pertaining to sex hormones and the IVD, TMJ, or articular cartilage were identified and reviewed by two independent reviewers. ~3900 articles were identified in our initial search, and after review, ~140 were identified to be relevant to our tissues of interest and the effects of sex hormones.

Results

Within all joint tissues investigated here, there were limited investigations on the effects of testosterone. Studies reported here for these tissues indicate that sex hormones are likely beneficial in the context of age-associated joint diseases, but there are important limitations to how this translates to the clinic given that various animal models can display distinct responses to sex hormone exposure. Direct comparisons of sex hormone therapies are limited between biological sexes, but evidence indicates that the molecular responses are likely similar. Current evidence indicates that sex hormone exposure likely has anti-inflammatory effects within joint tissues at the level of gene and protein expression, but the mechanism is unknown.

Conclusion

Sex hormones such as testosterone and estrogen play an important role in inflammatory signaling within joint tissues, which could lead to novel interventions within the clinic for joint degeneration. However, understanding the biological mechanisms of hormones in these distinct tissues, between sexes, and with age is imperative for their proper implementation.

研究背景性激素在临床治疗肌肉骨骼疾病中的应用越来越普遍。尽管如此,性激素在各种关节组织(如椎间盘(IVD)、颞下颌关节(TMJ)和关节软骨)中的作用仍然知之甚少。在这里,我们采用数据库搜索策略,通过范围审查来严格检查该领域的可用文献。方法采用四步方案,由两名独立审稿人对性激素与IVD、TMJ或关节软骨相关的主要研究文章进行鉴定和审查。在我们最初的搜索中发现了约3900篇文章,经过审查,约140篇被确定与我们感兴趣的组织和性激素的影响有关。结果在所有关节组织中,对睾酮的影响进行了有限的研究。这些组织的研究报告表明,性激素在与年龄相关的关节疾病中可能是有益的,但鉴于各种动物模型对性激素暴露表现出不同的反应,如何将其转化为临床存在重要的局限性。性激素治疗的直接比较在生理性别之间是有限的,但证据表明分子反应可能是相似的。目前的证据表明,性激素暴露可能在基因和蛋白质表达水平上对关节组织具有抗炎作用,但其机制尚不清楚。结论睾酮、雌激素等性激素在关节组织炎症信号传导中发挥重要作用,为临床治疗关节退变提供了新的干预手段。然而,了解激素在这些不同组织、性别和年龄之间的生物学机制,对于它们的正确实施是必要的。
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引用次数: 0
Relationship Between Lumbar Multifidus Morphometry and Pain/Disability in Individuals With Chronic Nonspecific Low Back Pain After Considering Demographics, Fear-Avoidance Beliefs, Insomnia, and Spinal Degenerative Changes 考虑人口统计学、恐惧回避信念、失眠和脊柱退行性改变后,腰椎多裂肌形态测定与慢性非特异性腰痛患者疼痛/残疾的关系
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-05-15 DOI: 10.1002/jsp2.70071
Sabina M. Pinto, Jason P. Y. Cheung, Dino Samartzis, Jaro Karppinen, Yong-Ping Zheng, Marco Y. C. Pang, Maryse Fortin, Arnold Y. L. Wong

Background

Although individuals with chronic low back pain (CLBP) show increased fatty infiltration in the lumbar multifidus muscle (LMM), it remains unclear whether LMM changes are related to clinical outcomes (such as pain and disability) after considering confounders (spinal phenotypes, fear-avoidance beliefs [FABs] and insomnia). This study examined: (1) differences in confounders and LMM characteristics between individuals with and without CLBP; and (2) associations between confounders, LMM parameters, and clinical outcomes in the CLBP group alone.

Methods

Participants (CLBP = 70 and asymptomatic people = 67) underwent lumbar magnetic resonance imaging. Outcome measures comprised the numeric pain rating scale, the Roland–Morris Disability Questionnaire, the Fear-Avoidance Beliefs Questionnaire (FABQ), and the Insomnia Severity Index (ISI) Scale. LMM morphometry at L3-S1 (cross-sectional area, total volume, and fatty infiltration) was measured using a customized MATLAB program. Spinal phenotypes (disc degeneration, high-intensity zones, Modic changes [MCs], Schmorl's nodes, facet joint degeneration [FJD], and facet tropism [FT]) were scored. The between-group differences were analyzed using linear mixed models and chi-squared/Fisher's exact tests. Univariate and multivariate analyses evaluated associations between clinical outcomes and other outcome measures in the CLBP group.

Results

The CLBP group demonstrated more severe disc degeneration and FJD at all levels, and greater FT at L5/S1 than asymptomatic participants (p < 0.05). The average LMM total volume at L3/4 and the percentage of fatty infiltration in LMM in the L3-S1 region were greater in the CLBP group than in asymptomatic counterparts (p < 0.05). The presence of MC at L4 and FJD at L4/5 and L4-S1 was significantly related to pain intensity in the CLBP group. Similarly, FABQ-Work and ISI scores were significantly related to pain intensity (explaining 37% of the variance in pain).

Conclusions

The CLBP group displays more fatty infiltration in the LMM, but their LMM morphometric parameters are unrelated to pain/disability after considering spinal phenotypes, FABs, and insomnia.

虽然慢性腰痛(CLBP)患者腰多裂肌(LMM)脂肪浸润增加,但在考虑混杂因素(脊柱表型、恐惧回避信念[FABs]和失眠)后,LMM的改变是否与临床结果(如疼痛和残疾)相关尚不清楚。本研究考察了:(1)有CLBP和无CLBP个体之间混杂因素和LMM特征的差异;(2)单独CLBP组混杂因素、LMM参数和临床结果之间的关系。方法参与者(CLBP = 70,无症状者= 67)行腰椎磁共振成像。结果测量包括数值疼痛评定量表、Roland-Morris残疾问卷、恐惧-回避信念问卷(FABQ)和失眠严重程度指数(ISI)量表。使用定制的MATLAB程序测量L3-S1的LMM形态(横截面积、总体积和脂肪浸润)。对脊柱表型(椎间盘退变、高强度区、Modic改变[MCs]、Schmorl's淋巴结、小关节退变[FJD]和小关节向性[FT])进行评分。采用线性混合模型和卡方/费雪精确检验分析组间差异。单因素和多因素分析评估了CLBP组临床结果和其他结果测量之间的关系。结果与无症状组相比,CLBP组表现出更严重的椎间盘退变和FJD, L5/S1的FT更大(p < 0.05)。CLBP组LMM L3/4区平均总容积及LMM L3-S1区脂肪浸润百分比均高于无症状组(p < 0.05)。CLBP组L4的MC和L4/5和L4- s1的FJD的存在与疼痛强度显著相关。同样,FABQ-Work和ISI分数与疼痛强度显著相关(解释了37%的疼痛差异)。结论CLBP组腰mm中脂肪浸润较多,但考虑到脊柱表型、fab和失眠,其腰mm形态计量参数与疼痛/残疾无关。
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引用次数: 0
Correction to “Gut Microbiome and Metabolome Changes in Chronic Low Back Pain Patients With Vertebral Bone Marrow Lesions” 对“慢性腰痛伴椎体骨髓病变患者肠道微生物组和代谢组变化”的修正
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-05-15 DOI: 10.1002/jsp2.70074

W. Li, J. Tu, J. Zheng, et al., Gut Microbiome and Metabolome Changes in Chronic Low Back Pain Patients With Vertebral Bone Marrow Lesions. JOR Spine 8 (2025): e70042, https://doi.org/10.1002/jsp2.70042

In the article cited above, Affiliations 8 and 9 were mistakenly merged. This has now been corrected, and 16 author affiliations are now shown.

We apologize for this error.

李伟,涂军,郑军,等。慢性腰痛伴椎体骨髓病变患者肠道微生物组和代谢组的变化。JOR Spine 8 (2025): e70042, https://doi.org/10.1002/jsp2.70042In上面引用的文章,附属机构8和9被错误地合并了。现在已经更正了,现在显示了16个作者的从属关系。我们为这个错误道歉。
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引用次数: 0
Intervertebral Lumbar Spine Kinematics in Chronic Low Back Pain Patients Measured Using Biplane Radiography 用双翼x线摄影测量慢性腰痛患者腰椎间段的运动学
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-05-14 DOI: 10.1002/jsp2.70069
William Anderst, C. James Kim, Kevin M. Bell, Tom Gale, Cate Gray, Carol M. Greco, Clarissa LeVasseur, Gina McKernan, Sabreen Megherhi, Charity G. Patterson, Sara R. Piva, Caroline Pellegrini, Michael J. Schneider, Joseph Shoemaker, Patrick Smith, Nam V. Vo, Gwendolyn A. Sowa
<div> <section> <h3> Background</h3> <p>Chronic low back pain (cLBP) presents as a heterogeneous condition, making diagnosis and treatment challenging. Lumbar spine intervertebral kinematics may provide an objective assessment of patients with cLBP that may be used to inform treatment decisions and evaluate the efficacy of interventions. The purpose of this study was to provide a quantitative description of intervertebral motion in the lumbar spine during flexion/extension (F/E) and lateral bending (LB) in individuals with cLBP.</p> </section> <section> <h3> Methods</h3> <p>Data from 125 individuals is included in this analysis (M: 53; F: 72; <i>n</i> = 66 < 60 years of age; average BMI: 25.7 ± 3.6 kg/m<sup>2</sup>). Dynamic biplane radiography (DBR) and a validated volumetric model-based tracking system were used to assess intervertebral motion at every lumbar level (L1-L2 through L5-S1) during active F/E and LB movements in individuals with cLBP. The outcome measures were the intervertebral translation and rotation range of motion (ROM), the contribution of each motion segment to lumbar motion, the anterior–posterior slip per degree of flexion (SPDF), and trial-to-trial repeatability as assessed by the standard deviation in continuous kinematics waveforms over 3 trials of each movement. Outcomes were calculated for the entire group as well as for the subgroups of men, women, individuals less than 60 years of age, and individuals 60 or more years of age.</p> </section> <section> <h3> Results</h3> <p>The mean intervertebral F/E ROM progressively increased from 6.8° ± 3.1° at the L1-L2 through the L4-L5 motion segments, then decreased from 9.7° ± 5.2° at L4-L5 to 8.4° ± 4.9° at L5-S1. However, substantial variability among individuals was observed, and only 7 participants (5.6%) followed this ROM pattern. The mean intervertebral LB ROM increased from 8.8° ± 3.2° at L1-L2 to 9.1° ± 4.2° at L2-L3 and then progressively decreased from the L2-L3 through the L5-S1 motion segments to 2.7° ± 1.8°. However, only 13 participants (10.4%) followed this ROM pattern. On average, the L1-L2, L2-L3, and L5-S1 motion segments were the main contributors to F/E when the torso was near the upright neutral position. L2-L3, L3-L4, and L4-L5 were the main contributors to midrange flexion and extension, and L3-L4, L4-L5, and L5-S1 were the main contributors to lumbar motion when the trunk was near full flexion. L1-L2 and L2-L3 were the main contributors to lumbar LB near the neutral position and through the midrange. The contributions from L4-L5 and L5-S1 peaked at the neutral position and at maximum bending. SPDF was similar in the L1-L2, L2-L3, and L3-L4 motion segmen
背景:慢性腰痛(cLBP)是一种异质性疾病,使得诊断和治疗具有挑战性。腰椎椎间运动学可以为cLBP患者提供客观评估,可用于指导治疗决策和评估干预措施的有效性。本研究的目的是提供cLBP患者在屈伸(F/E)和侧屈(LB)期间腰椎椎间运动的定量描述。方法125例个体资料纳入分析(M: 53;F: 72;N = 66 <; 60岁;平均BMI: 25.7±3.6 kg/m2)。动态双平面x线摄影(DBR)和基于体积模型的有效跟踪系统用于评估cLBP患者在主动F/E和LB运动期间每个腰椎水平(L1-L2至L5-S1)的椎间运动。结果测量是椎间平移和旋转运动范围(ROM),每个运动节段对腰椎运动的贡献,每屈曲度的前后滑移(SPDF),以及通过3次连续运动波形的标准差评估的试验对试验的重复性。计算整个组的结果,以及男性、女性、小于60岁的个体和大于60岁的个体的亚组结果。结果平均椎间F/E ROM从L1-L2到L4-L5运动节段的6.8°±3.1°逐渐增加,然后从L4-L5的9.7°±5.2°下降到L5-S1的8.4°±4.9°。然而,观察到个体之间存在很大的差异,只有7名参与者(5.6%)遵循这种ROM模式。平均椎间LB ROM从L1-L2的8.8°±3.2°增加到L2-L3的9.1°±4.2°,然后从L2-L3通过L5-S1运动节段逐渐减少到2.7°±1.8°。然而,只有13名参与者(10.4%)遵循这种ROM模式。平均而言,当躯干接近直立中立位时,L1-L2、L2-L3和L5-S1运动节段是F/E的主要贡献者。L2-L3、L3-L4和L4-L5是中屈曲和伸展的主要贡献者,而L3-L4、L4-L5和L5-S1是躯干接近完全屈曲时腰椎运动的主要贡献者。L1-L2和L2-L3是腰椎LB的主要贡献者。L4-L5和L5-S1的贡献在中性位置和最大弯曲时达到峰值。SPDF在L1-L2、L2-L3和L3-L4运动节段相似,但在L4-L5运动节段较少。与其他运动节段相比,L5-S1 SPDF具有个体间高变异性的特点。在F/E和LB期间,在运动学波形上所有点的主要运动平面上的椎间旋转的平均试验对试验的重复性范围为0.3°至0.7°,涵盖所有运动节段。结论本研究证明了cLBP患者腰椎椎间运动的异质性。需要进一步的研究来确定cLBP患者的运动学与其他生物学、行为和临床特征之间的机制联系,并确定哪些运动学特征对cLBP患者的治疗方法有用。
{"title":"Intervertebral Lumbar Spine Kinematics in Chronic Low Back Pain Patients Measured Using Biplane Radiography","authors":"William Anderst,&nbsp;C. James Kim,&nbsp;Kevin M. Bell,&nbsp;Tom Gale,&nbsp;Cate Gray,&nbsp;Carol M. Greco,&nbsp;Clarissa LeVasseur,&nbsp;Gina McKernan,&nbsp;Sabreen Megherhi,&nbsp;Charity G. Patterson,&nbsp;Sara R. Piva,&nbsp;Caroline Pellegrini,&nbsp;Michael J. Schneider,&nbsp;Joseph Shoemaker,&nbsp;Patrick Smith,&nbsp;Nam V. Vo,&nbsp;Gwendolyn A. Sowa","doi":"10.1002/jsp2.70069","DOIUrl":"https://doi.org/10.1002/jsp2.70069","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Chronic low back pain (cLBP) presents as a heterogeneous condition, making diagnosis and treatment challenging. Lumbar spine intervertebral kinematics may provide an objective assessment of patients with cLBP that may be used to inform treatment decisions and evaluate the efficacy of interventions. The purpose of this study was to provide a quantitative description of intervertebral motion in the lumbar spine during flexion/extension (F/E) and lateral bending (LB) in individuals with cLBP.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Data from 125 individuals is included in this analysis (M: 53; F: 72; &lt;i&gt;n&lt;/i&gt; = 66 &lt; 60 years of age; average BMI: 25.7 ± 3.6 kg/m&lt;sup&gt;2&lt;/sup&gt;). Dynamic biplane radiography (DBR) and a validated volumetric model-based tracking system were used to assess intervertebral motion at every lumbar level (L1-L2 through L5-S1) during active F/E and LB movements in individuals with cLBP. The outcome measures were the intervertebral translation and rotation range of motion (ROM), the contribution of each motion segment to lumbar motion, the anterior–posterior slip per degree of flexion (SPDF), and trial-to-trial repeatability as assessed by the standard deviation in continuous kinematics waveforms over 3 trials of each movement. Outcomes were calculated for the entire group as well as for the subgroups of men, women, individuals less than 60 years of age, and individuals 60 or more years of age.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The mean intervertebral F/E ROM progressively increased from 6.8° ± 3.1° at the L1-L2 through the L4-L5 motion segments, then decreased from 9.7° ± 5.2° at L4-L5 to 8.4° ± 4.9° at L5-S1. However, substantial variability among individuals was observed, and only 7 participants (5.6%) followed this ROM pattern. The mean intervertebral LB ROM increased from 8.8° ± 3.2° at L1-L2 to 9.1° ± 4.2° at L2-L3 and then progressively decreased from the L2-L3 through the L5-S1 motion segments to 2.7° ± 1.8°. However, only 13 participants (10.4%) followed this ROM pattern. On average, the L1-L2, L2-L3, and L5-S1 motion segments were the main contributors to F/E when the torso was near the upright neutral position. L2-L3, L3-L4, and L4-L5 were the main contributors to midrange flexion and extension, and L3-L4, L4-L5, and L5-S1 were the main contributors to lumbar motion when the trunk was near full flexion. L1-L2 and L2-L3 were the main contributors to lumbar LB near the neutral position and through the midrange. The contributions from L4-L5 and L5-S1 peaked at the neutral position and at maximum bending. SPDF was similar in the L1-L2, L2-L3, and L3-L4 motion segmen","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949817","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
Mechanisms and Therapeutic Strategies of Macrophage Polarization in Intervertebral Disc Degeneration 巨噬细胞极化在椎间盘退变中的作用机制及治疗策略
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-05-14 DOI: 10.1002/jsp2.70065
Kaiyuan Zheng, Siyu Wang, Meng Deng, Yaomin Luo, Wen Li, Lianlin Zeng, Yinxu Wang

Background

Intervertebral disc degeneration (IVDD) is a leading cause of low back pain (LBP), contributing significantly to global disability and productivity loss. Its pathogenesis involves complex processes, including inflammation, cellular senescence, angiogenesis, fibrosis, neural ingrowth, and sensitization. Emerging evidence highlights macrophages as central immune regulators infiltrating degenerated discs, with macrophage polarization implicated in IVDD progression. However, the mechanisms linking macrophage polarization to IVDD pathology remain poorly elucidated.

Methods

A comprehensive literature review was conducted by searching major databases (PubMed, Web of Science, and Scopus) for studies published in the last decade (2014–2024). Keywords included “intervertebral disc degeneration,” “macrophage polarization,” “inflammation,” “senescence,” and “therapeutic strategies.” Relevant articles were selected, analyzed, and synthesized to evaluate the role of macrophage polarization in IVDD.

Results

Macrophage polarization dynamically influences IVDD through multiple pathways. Pro-inflammatory M1 macrophages exacerbate disc degeneration by amplifying inflammatory cytokines (e.g., TNF-α, IL-1β), promoting cellular senescence, and stimulating abnormal angiogenesis and neural ingrowth. In contrast, anti-inflammatory M2 macrophages may mitigate degeneration by suppressing inflammation and enhancing tissue repair. Therapeutic strategies targeting macrophage polarization include pharmacological agents (e.g., cytokines, small-molecule inhibitors), biologic therapies, gene editing, and physical interventions. Challenges persist, such as incomplete understanding of polarization triggers, lack of targeted delivery systems, and limited translational success in preclinical models.

Conclusion

Macrophage polarization is a pivotal regulator of IVDD pathology, offering promising therapeutic targets. Future research should focus on elucidating polarization mechanisms, optimizing spatiotemporal control of macrophage phenotypes, and developing personalized therapies. Addressing these challenges may advance innovative strategies to halt or reverse IVDD progression, ultimately improving clinical outcomes for LBP patients.

背景椎间盘退变(IVDD)是腰痛(LBP)的主要原因,对全球残疾和生产力损失有重要影响。其发病机制涉及复杂的过程,包括炎症、细胞衰老、血管生成、纤维化、神经向内生长和致敏。新出现的证据表明巨噬细胞是浸润变性椎间盘的中枢免疫调节因子,巨噬细胞极化与IVDD进展有关。然而,巨噬细胞极化与IVDD病理之间的联系机制尚不清楚。方法通过检索PubMed、Web of Science、Scopus等主要数据库,检索近十年(2014-2024)发表的相关文献。关键词包括“椎间盘退变”、“巨噬细胞极化”、“炎症”、“衰老”和“治疗策略”。通过对相关文献的选取、分析和综合,来评价巨噬细胞极化在IVDD中的作用。结果巨噬细胞极化通过多种途径动态影响IVDD。促炎M1巨噬细胞通过放大炎性细胞因子(如TNF-α, IL-1β),促进细胞衰老,刺激异常血管生成和神经向内生长,从而加剧椎间盘退变。相反,抗炎M2巨噬细胞可能通过抑制炎症和增强组织修复来减轻变性。针对巨噬细胞极化的治疗策略包括药物(如细胞因子、小分子抑制剂)、生物疗法、基因编辑和物理干预。挑战仍然存在,例如对极化触发因素的不完全理解,缺乏靶向递送系统,以及临床前模型的有限转化成功。结论巨噬细胞极化是IVDD病理的关键调节因子,提供了有希望的治疗靶点。未来的研究应集中于阐明极化机制,优化巨噬细胞表型的时空控制,以及开发个性化的治疗方法。解决这些挑战可能会推进创新策略,以阻止或逆转IVDD的进展,最终改善LBP患者的临床结果。
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引用次数: 0
Human Disc Degeneration Is Accompanied by a Loss of Anterior Annulus Fibrosus Interlamellar Matrix Integrity as Assessed by Peel Tests 人椎间盘退变伴随着前纤维环板间基质完整性的丧失,通过皮试验评估
IF 3.4 3区 医学 Q1 ORTHOPEDICS Pub Date : 2025-05-14 DOI: 10.1002/jsp2.70067
Manmeet S. Dhiman, Mohammed A. Salaam, Taylor J. Bader, Fred Nicholls, W. Bradley Jacobs, Kenneth C. Thomas, Jacques Bouchard, Paul T. Salo, David A. Hart, Ganesh Swamy, Neil A. Duncan

Introduction

Disc degeneration (DD) is accompanied by biomechanical changes in the intervertebral discs. The lamellae of the annulus fibrosus (AF) are interconnected through the interlamellar matrix (ILM). The ILM contains interlamellar cross-bridges, connecting the lamellae radially in three dimensions. Weakening of the ILM and the cross-bridges could contribute to delamination between the lamellae, reducing their ability to resist loads and thus contributing to loss of AF integrity associated with the development and progression of degeneration. The objective of the present study was to quantify the differences in interlamellar mechanical properties of fresh AF samples from surgical DD individuals compared to AF samples from non-DD donors.

Methods

An interlamellar peel test was performed on fresh AF tissue collected from DD surgeries (n = 36) and non-DD organ donors (n = 13). The tissue was peeled at 0.5 mm/s until complete separation. Interlamellar mechanical properties were calculated from the force-displacement curve.

Results

Samples from DD individuals had lower Peel Stiffness (p = 0.001), Peel Strength (p = 0.001), Peel Toughness (p = 0.0009), and Standard Deviation of the Peel Stress (p = 0.02) compared to the tissue from non-DD organ donors. Age had moderate negative correlations with Peel Stiffness (R = −0.59), Peel Strength (R = −0.66), and Peel Toughness (R = −0.69) for non-DD samples only.

Discussion

The mechanical integrity of the ILM was determined to be lower in surgical DD individuals compared to non-DD donors. Aging alone may not have affected the results, and rather, loss of the integrity of ILM during disease progression appeared to have significantly contributed to the differences observed. This study provides new mechanical insights into the delamination often observed in the AF of surgical DD individuals. Future biochemical and immunolocalization studies, integrated with mechanical data, will aim to understand the role of collagen and elastin structure and composition in the decreased mechanical integrity of affected tissues.

椎间盘退变(DD)伴随着椎间盘的生物力学变化。纤维环(AF)的片层通过层间基质(ILM)相互连接。ILM包含层间交叉桥,在三维空间中径向连接片层。ILM和交叉桥的减弱可能导致片层之间的分层,降低其抵抗载荷的能力,从而导致与退化的发生和进展相关的AF完整性丧失。本研究的目的是量化来自外科DD患者的新鲜房颤样本与来自非DD供者的房颤样本的板间力学特性的差异。方法采用层间剥离试验对DD手术患者(36例)和非DD供者(13例)的新鲜房颤组织进行分析。以0.5 mm/s的速度剥皮,直至完全分离。根据力-位移曲线计算了层间力学性能。结果与非DD器官供体相比,DD个体的剥离刚度(p = 0.001)、剥离强度(p = 0.001)、剥离韧性(p = 0.0009)和剥离应力的标准差(p = 0.02)较低。年龄仅与非dd样品的剥离刚度(R = - 0.59)、剥离强度(R = - 0.66)和剥离韧性(R = - 0.69)呈中等负相关。与非DD供者相比,手术DD供者的ILM机械完整性较低。衰老本身可能不会影响结果,相反,在疾病进展过程中ILM完整性的丧失似乎显著地促成了观察到的差异。这项研究为外科DD患者房颤中经常观察到的分层提供了新的力学见解。未来的生化和免疫定位研究,结合力学数据,将旨在了解胶原蛋白和弹性蛋白的结构和组成在受损组织机械完整性下降中的作用。
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引用次数: 0
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JOR Spine
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