JOR Spine最新文献_第2页

Comparative Finite Element Analysis of Denosumab and Bazedoxifene on Pedicle Screw Stability in Osteoporotic Spines Denosumab与Bazedoxifene对骨质疏松症椎弓根螺钉稳定性的有限元对比分析。

IF 3.9 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-12-09 DOI: 10.1002/jsp2.70147

Tomoyuki Asada, Soji Tani, Tomoko Towatari, Mahoko Ishikawa, Philip Varnadore, Yoshifumi Kudo, Peter G. Passias, Benjamin A. Alman, Koji Ishikawa

Introduction

Pedicle screw fixation in osteoporotic spines remains challenging. Bazedoxifene (BZA) and denosumab (Dmab) are widely used agents for osteoporosis, but their comparative effects on spinal instrumentation are not well understood. This study aimed to evaluate the effects of BZA and Dmab on biomechanical parameters of spinal instrumentation using finite element analysis (FEA).

Methods

In this prospective, open-label study, postmenopausal women with primary osteoporosis were assigned to receive either BZA (daily oral, 20 mg) or Dmab (subcutaneous, 60 mg every 6 months) for 12 months. FEA models of the L4 vertebra were generated from CT scans using a calibration phantom (Mindways, Austin, TX, USA). Vertebral compression force was evaluated to represent overall vertebral strength. Pedicle screw fixation strength was assessed under axial (pullout strength) and non-axial directional forces (cranial, caudal, lateral, medial). Inverse probability of treatment weighting (IPTW) and multivariable regression were used to balance baseline differences and compare biomechanical outcomes between groups.

Results

Thirty patients were enrolled (15 per group); the final analysis included 12 in the BZA group and 13 in the Dmab group. Compared to BZA, Dmab significantly improved compression strength (adjusted mean difference: 8.1% [95% CI, 0.9–15.3], p = 0.030) and pullout strength (15.8% [95% CI, 6.2–25.4], p = 0.003). Directional FEA revealed greater resistance to cranial (17.4% [95% CI, 4.9–30.0], p = 0.009) and lateral (10.8% [95% CI, 0.9–20.8], p = 0.035) loading with Dmab, while no significant difference was observed in caudal- and medial-directed force.

Conclusion

Finite element modeling suggested that Dmab enhanced pedicle screw fixation more effectively than BZA, particularly against axial and cranial/lateral-directed forces. These biomechanical differences underscore the potential advantage of Dmab in preoperative osteoporosis management to improve pedicle screw stability.

导读：椎弓根螺钉固定在骨质疏松的脊柱仍然具有挑战性。Bazedoxifene （BZA）和denosumab （Dmab）是骨质疏松症广泛使用的药物，但它们对脊柱内固定的比较效果尚不清楚。本研究旨在通过有限元分析（finite element analysis， FEA）评估BZA和Dmab对脊柱内固定物生物力学参数的影响。方法：在这项前瞻性、开放标签研究中，患有原发性骨质疏松症的绝经后妇女被分配接受BZA（每日口服，20毫克）或Dmab（皮下注射，每6个月60毫克），为期12个月。使用校准模体（Mindways, Austin， TX， USA）通过CT扫描生成L4椎体的有限元模型。评估椎体压缩力以代表整体椎体强度。在轴向（拔出强度）和非轴向方向力（颅、尾、外侧、内侧）下评估椎弓根螺钉固定强度。使用治疗加权逆概率（IPTW）和多变量回归来平衡基线差异并比较组间的生物力学结果。结果：30例患者入组（每组15例）；最终分析BZA组12例，Dmab组13例。与BZA相比，Dmab显著提高了抗压强度（调整后的平均差值：8.1% [95% CI, 0.9-15.3], p = 0.030）和拉拔强度（15.8% [95% CI, 6.2-25.4], p = 0.003）。定向有限元分析显示，Dmab对颅骨（17.4% [95% CI, 4.9-30.0], p = 0.009）和外侧（10.8% [95% CI, 0.9-20.8], p = 0.035）载荷的抵抗更大，而在尾侧和内侧定向力方面没有观察到显著差异。结论：有限元模型表明，Dmab比BZA更有效地增强了椎弓根螺钉的固定，特别是在轴向和颅/侧向力的作用下。这些生物力学差异强调了Dmab在术前骨质疏松管理中提高椎弓根螺钉稳定性的潜在优势。

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引用次数: 0

Development and Characterization of a Tunable PDMS Substrate Model for Investigating Elastic Properties and Mechanical Stretching in Intervertebral Disc Cells 用于研究椎间盘细胞弹性特性和机械拉伸的可调谐PDMS底物模型的开发和表征。

IF 3.9 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-12-08 DOI: 10.1002/jsp2.70140

Johannes Hasler, Mikkael Lamoca, Kory Schimmelpfennig, Shuhuan Zhang, Wolfgang Hitzl, Sami Farajollahi, Vinay V. Abhyankar, Christopher L. Lewis, Rui Liu, Karin Wuertz-Kozak

Background

Aberrant mechanical loading and altered extracellular matrix (ECM) composition favor catabolic cell responses, contributing to intervertebral disc (IVD) degeneration and ultimately impairing the integrity of the annulus fibrosus (AF). This highlights the need for new in vitro models to investigate the interplay of mechanical loading and cell–substrate interactions. Therefore, this study introduces a tunable stretching chamber platform to simultaneously study both factors in AF degeneration.

Methods

Tunable PDMS substrates were fabricated by adjusting ratios of Sylgard 184 and Sylgard 527, enabling molding into stretching chambers or well plates. Substrates underwent mechanical, optical, and chemical characterization. Bovine AF cells were seeded onto the substrates and cultured under static conditions or subjected to cyclic strain (8% strain at 1 Hz). Substrate biocompatibility and cell morphology were assessed over 72 h in static cultures. Dynamic responses were assessed by cell viability and alignment. Digital image correlation (DIC) was employed to assess surface strain in custom-designed and commercial (STREX) stretching chambers at strains between 8% and 20%.

Results

PDMS formulations resulted in a stiffness (E modulus) range of 8.72–238.00 kPa, demonstrating distinct viscoelastic profiles. All substrate formulations supported AF cell adhesion and viability. DIC analysis revealed non-uniform axial and transverse strain distributions on membrane surfaces. Cyclic stretching showed that cells maintained viability up to 14 h. Additionally, cells responded to the applied strain by perpendicular alignment to the stretch axis at 6 h.

Conclusions

The PDMS-based stretching platform offers a biocompatible and tunable mechanical environment that mimics physiological and pathophysiological elastic properties. It enables systematic investigations on how elastic properties and mechanical strain modulate AF cell behavior in IVD disease progression. Finally, this study raises the awareness of non-uniform and transverse strain components within the stretching chambers and highlights the discrepancy of effective strain transfer to the cell interaction surface.

背景：异常的机械负荷和改变的细胞外基质（ECM）组成有利于分解代谢细胞的反应，导致椎间盘（IVD）退变，最终损害纤维环（AF）的完整性。这突出了需要新的体外模型来研究机械载荷和细胞-底物相互作用的相互作用。因此，本研究引入可调谐拉伸室平台，同时研究房颤退变的两个因素。方法：通过调节Sylgard 184和Sylgard 527的比例制备可调PDMS基底，使其成型为拉伸室或孔板。衬底经过机械、光学和化学表征。将牛心房颤动细胞接种于底物上，在静态条件下或循环应变（8%应变，1hz）下培养。在静态培养72 h后评估底物的生物相容性和细胞形态。通过细胞活力和排列来评估动态响应。采用数字图像相关（DIC）来评估定制设计和商用（STREX）拉伸室在8%至20%应变范围内的表面应变。结果：PDMS配方产生的刚度（E模量）范围为8.72-238.00 kPa，表现出明显的粘弹性剖面。所有底物制剂都支持AF细胞的粘附和活力。DIC分析显示膜表面的轴向和横向应变分布不均匀。循环拉伸显示细胞存活时间可达14小时。此外，细胞对施加的应变作出反应，在6小时垂直于拉伸轴。结论：基于pdms的拉伸平台提供了一个生物相容性和可调的机械环境，模拟了生理和病理生理的弹性特性。它可以系统地研究弹性特性和机械应变如何调节房颤细胞在IVD疾病进展中的行为。最后，本研究提高了对拉伸室内非均匀应变和横向应变分量的认识，并强调了有效应变传递到细胞相互作用表面的差异。

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引用次数: 0

The Prognostic Significance of LINC00638 in Lumbar Disc Herniation and Its Effect on Senescence of Nucleus Pulposus Cells LINC00638对腰椎间盘突出症的预后意义及其对髓核细胞衰老的影响

IF 3.9 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-12-05 DOI: 10.1002/jsp2.70138

Zhen Wang, Jichen Liu, Yanhua Sun, Haishan Xu, Wei He, Shaowei Xu, Xijing He

Background

Lumbar disc herniation (LDH) is a common degenerative spinal disorder that severely impacts patients' quality of life. This study investigated the prognostic values of the lncRNA LINC00638 in LDH and its regulatory role in the senescence of human nucleus pulposus cells (hNPCs).

Methods

Serum was collected from 93 LDH patients and 108 healthy individuals (matched age and gender). RT-qPCR was used to detect LINC00638 and miR-185-5p expression. The diagnostic and prognostic significance was analyzed using ROC and logistic regression. The hNPCs senescence model induced by 50 ng/mL TNF-α was established to explore the effects of LINC00638 overexpression (alone or combined with miR-185-5p) on cell proliferation, apoptosis, senescence, inflammation, and oxidative stress.

Results

Serum LINC00638 levels in LDH patients gradually decreased with disease progression (p < 0.05) and were significantly correlated with VAS, JOA and ODI scores (p < 0.001). Low LINC00638 expression was identified as a reliable diagnostic indicator for LDH (AUC = 0.828, sensitivity 70.97%, specificity 80.56%, p < 0.001) and an independent risk factor for poor prognosis (OR = 0.176, p = 0.009). Cellular experiments showed that LINC00638 overexpression significantly inhibited TNF-α-induced cell senescence (p < 0.01), while this inhibitory effect was reversed by miR-185-5p overexpression (p < 0.05).

Conclusions

Serum LINC00638 holds promise as a potential biomarker for the diagnosis and prognostic evaluation of LDH, closely reflecting disease severity. Furthermore, LINC00638 participates in regulating hNPCs' senescence and LDH progression by modulating miR-185-5p.

腰椎间盘突出症（LDH）是一种常见的退行性脊柱疾病，严重影响患者的生活质量。本研究探讨lncRNA LINC00638在LDH中的预后价值及其在人髓核细胞（hNPCs）衰老中的调节作用。方法收集LDH患者93例，健康人群108例（年龄、性别匹配）血清。RT-qPCR检测LINC00638和miR-185-5p的表达。采用ROC和logistic回归分析诊断和预后意义。建立50 ng/mL TNF-α诱导的hNPCs衰老模型，探讨LINC00638过表达（单独或联合miR-185-5p）对细胞增殖、凋亡、衰老、炎症和氧化应激的影响。结果LDH患者血清LINC00638水平随疾病进展逐渐降低（p < 0.05），并与VAS、JOA、ODI评分显著相关（p < 0.001）。LINC00638低表达是LDH的可靠诊断指标（AUC = 0.828，敏感性70.97%，特异性80.56%,p < 0.001），也是预后不良的独立危险因素（OR = 0.176, p = 0.009）。细胞实验表明，LINC00638过表达可显著抑制TNF-α-诱导的细胞衰老（p < 0.01），而miR-185-5p过表达可逆转这种抑制作用（p < 0.05）。结论血清LINC00638有望作为LDH诊断和预后评估的潜在生物标志物，密切反映疾病严重程度。此外，LINC00638通过调节miR-185-5p参与hNPCs衰老和LDH进展的调控。

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引用次数: 0

Thoracolumbar Biomechanical Analysis of Lenke Type 1 Adolescent Idiopathic Scoliosis Across Roussouly Classifications Lenke型青少年特发性脊柱侧凸跨Roussouly分类的胸腰椎生物力学分析。

IF 3.9 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-12-01 DOI: 10.1002/jsp2.70148

Zhihua Wu, Huantong Cheng, Jia He, Xiaowei Dai, Junyu He, De Liang, Xiaobing Jiang, Yueli Sun, Ruitao She, Yuanfang Lin, Ziyang Liang, Wei Wei

Background

Lenke type 1 is the most common adolescent idiopathic scoliosis (AIS), and its sagittal morphology critically influences progression and treatment. However, its biomechanical characteristics across Roussouly types remain unclear.

Purpose

To quantify the biomechanical responses of Lenke type 1 AIS under pure bending moments across different Roussouly classifications.

Methods

This study was based on a validated thoracolumbar finite element model. Using mesh morphing, spinal alignments and vertebral rotations were adjusted to construct finite element models of Lenke type 1 AIS with Roussouly types 1–4. Simulations were conducted under ±7.5 Nm pure bending moments for flexion-extension, lateral bending, and axial rotation. Spinal range of motion (ROM) and intervertebral disc loadings—including force, moment, and Von Mises stress—were quantified.

Results

Compared to the normal model, the AIS model showed asymmetrical total ROM at the T7–T12 segment, whereas the T1–S1 segment remained relatively symmetrical. At the T9–T10 and T12–L1 discs, shear and compressive forces increased markedly, with peak values of 197 N and secondary moments reaching ~2.8 Nm. Stress in the T9–T10 disc exhibited a distinct concave-side concentration, with the maximum Von Mises stress reaching 7.7 MPa. The T1–S1 ROM during extension, right bending, and right rotation in Roussouly 1 and 2 was ~10% greater than in Roussouly 3 and 4, with markedly higher shear and compressive forces (up to 50-fold) at the T6–T7 and T9–T10 discs. Regarding stress distribution, Von Mises stress at the T6–T7 and T9–T10 discs was higher in Roussouly 3 and 4, whereas stress at the T12–L1 disc was more pronounced in Roussouly 1 and 2.

Conclusion

The findings underscore the critical role of sagittal morphology in AIS biomechanics. Compared to Roussouly 1 and 2, Roussouly 3 and 4 exhibited reduced ROM, lower disc forces, and more favorable stress distributions, suggesting a biomechanically advantageous load-bearing pattern.

背景：Lenke 1型是最常见的青少年特发性脊柱侧凸（AIS），其矢状面形态对进展和治疗有重要影响。然而，其在Roussouly类型中的生物力学特征仍不清楚。目的：量化不同Roussouly分类下Lenke 1型AIS在纯弯矩作用下的生物力学响应。方法：本研究基于经验证的胸腰椎有限元模型。通过网格变形，调整脊柱对齐和椎体旋转，构建Lenke 1型AIS有限元模型，Roussouly类型1-4。在±7.5 Nm纯弯矩下进行了屈伸、侧向弯曲和轴向旋转的模拟。脊柱活动范围（ROM）和椎间盘负荷（包括力、力矩和Von Mises应力）被量化。结果：与正常模型相比，AIS模型在T7-T12节段呈现不对称的总ROM，而T1-S1节段保持相对对称。在T9-T10和T12-L1圆盘处，剪切力和压缩力显著增加，峰值为197 N，次弯矩达到~2.8 Nm。T9-T10椎间盘应力呈明显的凹侧集中，最大Von Mises应力达到7.7 MPa。Roussouly 1和2在伸展、右弯曲和右旋转时的T1-S1 ROM比Roussouly 3和4大10%，T6-T7和T9-T10椎间盘的剪切和压缩力明显更高（高达50倍）。应力分布方面，T6-T7和T9-T10椎间盘的Von Mises应力在Roussouly 3和4中较高，而T12-L1椎间盘的应力在Roussouly 1和2中更为明显。结论：矢状面形态学在AIS生物力学中的重要作用。与Roussouly 1和2相比，Roussouly 3和4表现出更小的ROM，更低的椎间盘力和更有利的应力分布，表明生物力学上有利的承重模式。

{"title":"Thoracolumbar Biomechanical Analysis of Lenke Type 1 Adolescent Idiopathic Scoliosis Across Roussouly Classifications","authors":"Zhihua Wu, Huantong Cheng, Jia He, Xiaowei Dai, Junyu He, De Liang, Xiaobing Jiang, Yueli Sun, Ruitao She, Yuanfang Lin, Ziyang Liang, Wei Wei","doi":"10.1002/jsp2.70148","DOIUrl":"10.1002/jsp2.70148","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lenke type 1 is the most common adolescent idiopathic scoliosis (AIS), and its sagittal morphology critically influences progression and treatment. However, its biomechanical characteristics across Roussouly types remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>To quantify the biomechanical responses of Lenke type 1 AIS under pure bending moments across different Roussouly classifications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study was based on a validated thoracolumbar finite element model. Using mesh morphing, spinal alignments and vertebral rotations were adjusted to construct finite element models of Lenke type 1 AIS with Roussouly types 1–4. Simulations were conducted under ±7.5 Nm pure bending moments for flexion-extension, lateral bending, and axial rotation. Spinal range of motion (ROM) and intervertebral disc loadings—including force, moment, and Von Mises stress—were quantified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to the normal model, the AIS model showed asymmetrical total ROM at the T7–T12 segment, whereas the T1–S1 segment remained relatively symmetrical. At the T9–T10 and T12–L1 discs, shear and compressive forces increased markedly, with peak values of 197 N and secondary moments reaching ~2.8 Nm. Stress in the T9–T10 disc exhibited a distinct concave-side concentration, with the maximum Von Mises stress reaching 7.7 MPa. The T1–S1 ROM during extension, right bending, and right rotation in Roussouly 1 and 2 was ~10% greater than in Roussouly 3 and 4, with markedly higher shear and compressive forces (up to 50-fold) at the T6–T7 and T9–T10 discs. Regarding stress distribution, Von Mises stress at the T6–T7 and T9–T10 discs was higher in Roussouly 3 and 4, whereas stress at the T12–L1 disc was more pronounced in Roussouly 1 and 2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The findings underscore the critical role of sagittal morphology in AIS biomechanics. Compared to Roussouly 1 and 2, Roussouly 3 and 4 exhibited reduced ROM, lower disc forces, and more favorable stress distributions, suggesting a biomechanically advantageous load-bearing pattern.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12668898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668501","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

Unveiling the Potential Mechanism of Asymmetric Fat Infiltration in Paraspinal Muscles of Adult Degenerative Scoliosis: The Role of the Hsa_circ_0006156/miR-122-5p/PPARA Regulatory Network 揭示成人退行性脊柱侧凸椎旁肌肉不对称脂肪浸润的潜在机制：Hsa_circ_0006156/miR-122-5p/PPARA调控网络的作用

IF 3.9 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-11-30 DOI: 10.1002/jsp2.70146

Xueneng Yang, Limin Guo, Jun Shu

Background

Paraspinal muscle degeneration, particularly fat infiltration, is a prominent feature of adult degenerative scoliosis (ADS), which impairs spinal stability, accelerates disease progression, and contributes to poor clinical outcomes. However, the underlying molecular mechanisms remain unclear. This study aims to investigate the role of the hsa_circ_0006156/miR-122-5p/PPARA regulatory axis in this process.

Methods

Paraspinal muscle fat infiltration was assessed by MRI in ADS patients and 40 age-matched controls. HE staining, Oil Red O staining, and RT-PCR were used to evaluate muscle structure and gene expression. Overexpression of hsa_circ_0006156 and inhibition of miR-122-5p were performed in primary multifidus muscle cells. Western blot and dual-luciferase reporter assays were used to verify the regulatory pathway.

Results

Paraspinal muscle fat infiltration was significantly increased in ADS patients and showed clear asymmetry. hsa_circ_0006156 was downregulated on the concave side. Its overexpression reduced lipid accumulation, downregulated adiponectin and perilipin, and increased PPARA expression. Bioinformatics analysis and luciferase assays confirmed miR-122-5p as a direct target of hsa_circ_0006156, and PPARA as a downstream gene of miR-122-5p. Inhibiting miR-122-5p reduced fat accumulation and increased PPARA expression. Co-transfection assays showed that hsa_circ_0006156 regulates lipid metabolism by sponging miR-122-5p and releasing its inhibition on PPARA.

Conclusion

Paraspinal muscles in ADS patients show marked fat infiltration with lateral asymmetry, especially on the concave side. hsa_circ_0006156 regulates lipid metabolism through the miR-122-5p/PPARA axis and reduces fat deposition, providing a potential molecular target for early diagnosis and intervention in ADS-related muscle degeneration.

背景：椎旁肌退变，尤其是脂肪浸润，是成人退行性脊柱侧凸（ADS）的一个显著特征，它损害脊柱稳定性，加速疾病进展，导致临床预后不良。然而，潜在的分子机制尚不清楚。本研究旨在探讨hsa_circ_0006156/miR-122-5p/PPARA调控轴在这一过程中的作用。方法：采用MRI评估ADS患者和40例年龄匹配的对照组的棘旁肌脂肪浸润情况。采用HE染色、油红O染色、RT-PCR检测肌肉结构及基因表达。在原代多裂肌细胞中过表达hsa_circ_0006156和抑制miR-122-5p。使用Western blot和双荧光素酶报告基因检测来验证调控途径。结果：ADS患者棘旁肌脂肪浸润明显增加，呈明显的不对称性。Hsa_circ_0006156在凹侧下调。其过表达减少脂质积累，下调脂联素和periilipin，增加PPARA表达。生物信息学分析和荧光素酶测定证实miR-122-5p是hsa_circ_0006156的直接靶点，PPARA是miR-122-5p的下游基因。抑制miR-122-5p减少脂肪积累，增加PPARA表达。共转染实验显示hsa_circ_0006156通过海绵化miR-122-5p并释放其对PPARA的抑制来调节脂质代谢。结论：ADS患者棘旁肌脂肪浸润明显，且外侧不对称，尤以凹侧为明显。hsa_circ_0006156通过miR-122-5p/PPARA轴调控脂质代谢，减少脂肪沉积，为ads相关肌肉变性的早期诊断和干预提供了潜在的分子靶点。

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引用次数: 0

Subject-Specific Musculoskeletal Modeling: The Future of Predicting and Preventing Proximal Junctional Failure in Adult Spinal Deformity 受试者特异性肌肉骨骼模型：预测和预防成人脊柱畸形近端连接功能衰竭的未来。

IF 3.9 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-11-30 DOI: 10.1002/jsp2.70142

Nima Ashjaee, Alexa Semonche, Anthony L. Mikula, Laszlo Kiss, Dennis E. Anderson, Dominika Ignasiak, Stephen H. M. Brown, John Street, Sidney Fels, Samuel R. Ward, Christopher Ames, Thomas R. Oxland

Background

Adult spinal deformity (ASD) is an increasingly prevalent disorder in the aging population. Surgical intervention is a common and generally effective treatment for severe cases. However, it is associated with relatively high rates of complications, one of the most common, and devastating of which is proximal junctional failure (PJF). PJF is characterized by symptomatic mechanical failure at the junction of the spinal fusion construct and the adjacent proximal mobile spinal segments, leading to a kyphotic deformity.

Current Limitations

The etiology of PJF remains a topic of ongoing investigation, with uncertainty surrounding the specific factors that predispose individual patients to this complication. Current predictive models primarily rely on radiographic parameters on standing X-rays to assess PJF risk, but their clinical utility remains limited. We contend that these models universally fail to adequately account for the role of paraspinal muscle function and dysfunction, iatrogenic surgical muscle injury, bone quality, integrity of the discoligamentous elements, and spinal kinetics.

Proposed Approach

Musculoskeletal modeling offers a powerful tool to enhance our understanding of human body kinetics and kinematics, including the complex biomechanical interactions in the spine. By integrating the biomechanical characteristics of bone and soft tissue into surgical treatment planning, we contend that subject-specific musculoskeletal modeling will improve PJF predictability, enable the explanation and interpretation of PJF, and ultimately optimize outcomes for patients undergoing surgery for ASD.

Conclusion

Subject-specific musculoskeletal modeling represents a critical opportunity to address the limitations of existing predictive systems and advance the field of ASD management.

背景：成人脊柱畸形（ASD）是老龄化人群中越来越普遍的疾病。手术干预是一种常见且通常有效的治疗重症病例的方法。然而，它与相对较高的并发症发生率相关，其中最常见和最具破坏性的是近端连接功能衰竭（PJF）。PJF的特点是脊柱融合结构和邻近近端可活动脊柱节段交界处出现症状性机械故障，导致后凸畸形。当前限制：PJF的病因学仍是一个正在进行的研究课题，不确定的具体因素使个体患者易患这种并发症。目前的预测模型主要依靠站立x光片的放射学参数来评估PJF的风险，但其临床应用仍然有限。我们认为，这些模型普遍未能充分考虑棘旁肌功能和功能障碍、医源性手术肌肉损伤、骨质量、韧带完整性和脊柱动力学的作用。建议方法：肌肉骨骼模型提供了一个强大的工具来增强我们对人体动力学和运动学的理解，包括脊柱中复杂的生物力学相互作用。通过将骨骼和软组织的生物力学特征整合到手术治疗计划中，我们认为，针对特定受试者的肌肉骨骼建模将提高PJF的可预测性，使PJF的解释和解释成为可能，并最终优化ASD手术患者的预后。结论：受试者特异性肌肉骨骼建模是解决现有预测系统局限性和推进ASD管理领域的关键机会。

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引用次数: 0

An Ex Vivo Model of Intervertebral Disc Degeneration for Assessing Retention of Injectable Cell-Based Grafts 椎间盘退变的离体模型用于评估可注射细胞基移植物的保留性

IF 3.9 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-11-26 DOI: 10.1002/jsp2.70144

Raphael Schmid, Janhavi Apte, Elias Schulze, Andrej Sirek, Günther Schäfer, Jessica Schäper, Francesco Santini, Simona Negoias, Andrea Barbero, Ivan Martin, Karoliina Pelttari, Stefan Schären, Olga Krupkova, Arne Mehrkens

Introduction

Cell therapies for painful intervertebral disc (IVD) degeneration (IDD) have not yet achieved widespread clinical adoption. Understanding therapeutic cell effects in native IVD remains challenging due to the complex IVD environment and limitations of current models. We present a physiologically relevant ex vivo model of IVD degeneration, which we employ to evaluate the retention of therapeutic cells in the IVD.

Methods

Bovine IVDs were cultured ex vivo for 14 days. IVD degeneration was induced under physiological loading by chondroitinase ABC (ChABC), or ChABC with pro-inflammatory cytokines (Infl) aiming to mimic IDD. The nucleus pulposus (NP) tissue integrity was characterized by T2 MRI and modified Thompson grading and compared with human IVDs of different ages. The onset of IDD in the bovine model was assessed by IL-8, MMP13, and COX-2 expression. Spheroids derived from mCherry-transduced human nasal chondrocytes (NCS) were injected into the NP. NCS retention within the IDD model was assessed by NCS ability to survive (c-caspase 3), localize (mCherry), and produce chondrogenic proteins (SOX-9, aggrecan).

Results

ChABC injection reduced water and proteoglycan content in the NP, resembling human age-related IVD degeneration. ChABC + Infl treatment led to a more pronounced loss of tissue integrity and upregulation of IL-8, MMP13, and COX-2, typically characterizing the transition to IDD. Upon injection into the IDD model, NCS localized in the NP, some remained viable, and maintained their chondrogenic features, demonstrating successful retention within the 7-day time frame.

Conclusion

We developed an ex vivo IVD model with a controlled and physiologically relevant environment and used it for assessing the retention of cell-based therapies for NP repair. The model recapitulated the progression of IVD degeneration, establishing its value as a preclinical research tool and reducing the reliance on animal studies during the early translational phase.

细胞疗法治疗疼痛性椎间盘（IVD）退变（IDD）尚未获得广泛的临床应用。由于复杂的IVD环境和现有模型的局限性，了解原生IVD中的治疗细胞效应仍然具有挑战性。我们提出了一个生理相关的体外IVD变性模型，我们用它来评估治疗细胞在IVD中的保留。方法采用体外培养法培养14 d。在生理负荷下，通过软骨素酶ABC （ChABC）或ChABC与促炎细胞因子（Infl）模拟IDD诱导IVD变性。采用T2 MRI和改良汤普森分级对髓核（NP）组织完整性进行了表征，并与不同年龄的人ivd进行了比较。通过IL-8、MMP13和COX-2的表达来评估牛IDD模型的发病情况。将mccherry转导的人鼻软骨细胞（NCS）衍生的球体注射到NP中。通过NCS存活（c-caspase 3）、定位（mCherry）和产生软骨蛋白（SOX-9、聚集蛋白）的能力来评估IDD模型中NCS的保留。结果ChABC注射液降低了NP中水分和蛋白聚糖的含量，类似于人类年龄相关性IVD变性。ChABC + Infl治疗导致更明显的组织完整性丧失和IL-8、MMP13和COX-2的上调，这是向IDD过渡的典型特征。注射到IDD模型后，NCS定位在NP中，一些仍然存活，并保持其软骨特征，在7天的时间内成功保留。我们建立了一个体外IVD模型，具有可控的和生理相关的环境，并使用它来评估基于细胞疗法的NP修复保留。该模型概括了IVD退行性变的进展，确立了其作为临床前研究工具的价值，并减少了早期转化阶段对动物研究的依赖。

{"title":"An Ex Vivo Model of Intervertebral Disc Degeneration for Assessing Retention of Injectable Cell-Based Grafts","authors":"Raphael Schmid, Janhavi Apte, Elias Schulze, Andrej Sirek, Günther Schäfer, Jessica Schäper, Francesco Santini, Simona Negoias, Andrea Barbero, Ivan Martin, Karoliina Pelttari, Stefan Schären, Olga Krupkova, Arne Mehrkens","doi":"10.1002/jsp2.70144","DOIUrl":"https://doi.org/10.1002/jsp2.70144","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Cell therapies for painful intervertebral disc (IVD) degeneration (IDD) have not yet achieved widespread clinical adoption. Understanding therapeutic cell effects in native IVD remains challenging due to the complex IVD environment and limitations of current models. We present a physiologically relevant ex vivo model of IVD degeneration, which we employ to evaluate the retention of therapeutic cells in the IVD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Bovine IVDs were cultured ex vivo for 14 days. IVD degeneration was induced under physiological loading by chondroitinase ABC (ChABC), or ChABC with pro-inflammatory cytokines (Infl) aiming to mimic IDD. The nucleus pulposus (NP) tissue integrity was characterized by T2 MRI and modified Thompson grading and compared with human IVDs of different ages. The onset of IDD in the bovine model was assessed by IL-8, MMP13, and COX-2 expression. Spheroids derived from mCherry-transduced human nasal chondrocytes (NCS) were injected into the NP. NCS retention within the IDD model was assessed by NCS ability to survive (c-caspase 3), localize (mCherry), and produce chondrogenic proteins (SOX-9, aggrecan).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ChABC injection reduced water and proteoglycan content in the NP, resembling human age-related IVD degeneration. ChABC + Infl treatment led to a more pronounced loss of tissue integrity and upregulation of IL-8, MMP13, and COX-2, typically characterizing the transition to IDD. Upon injection into the IDD model, NCS localized in the NP, some remained viable, and maintained their chondrogenic features, demonstrating successful retention within the 7-day time frame.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We developed an ex vivo IVD model with a controlled and physiologically relevant environment and used it for assessing the retention of cell-based therapies for NP repair. The model recapitulated the progression of IVD degeneration, establishing its value as a preclinical research tool and reducing the reliance on animal studies during the early translational phase.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626013","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

Evaluation of Lumbar Intervertebral Disc and Facet Joint Degeneration Using Histogram Analysis of T2 and T2* Values 用T2和T2*值直方图分析评价腰椎间盘和小关节退变

IF 3.9 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-11-26 DOI: 10.1002/jsp2.70141

Xiaoqing Liang, Yitong Li, Bowen Hou, Yan Xiong, John Morelli, Weiyin Vivian Liu, Xiaoming Li

Background

Lumbar facet joint (LFJ) and intervertebral disc (IVD) degeneration are the common causes of low back pain. The aim of this study is to explore the feasibility of histogram analysis of T2 and T2* values on grading LFJ and IVD degeneration and to examine the correlation between the LFJ and IVD in the degenerative process.

Methods

420 IVDs and 840 LFJs of 87 subjects were examined using T2WI, T2 and T2* mapping. All IVDs and LFJs were classified, respectively, according to the Pfirrmann and Weishaupt grade and grouped by patient age. Histogram-derived parameters based on T2 (T2-HPs) and T2* (T2*-HPs) values of IVDs and LFJs were compared among the different groups.

Results

The interobserver agreement for Pfirrmann grade was good (κ = 0.732), and moderate for Weishaupt grading (κ = 0.474). For patients under 39 years old, the degeneration incidence (DI) of LFJ was higher than IVD (χ² = 16.436, p < 0.001; χ² = 5.210, p = 0.022). In the 50–59 and 60–69 years groups, the DI of LFJ was statistically significantly lower than that of IVD (χ² = 14.915, p < 0.001; χ² = 13.174, p < 0.001). The interobserver reliability of histogram parameters for IVDs was good to excellent with ICCs ranging from 0.825 to 0.985, and poor to excellent for LFJs (0.302–0.945). All T2-HPs and T2*-HPs had the ability to distinguish normal IVDs from abnormal discs, with the AUC varying from 0.562 to 0.824. For T2-HPs, only SD and Entropy can not distinguish normal (Weishaupt grades 0 and 1) and abnormal (grades 2 and 3) LFJs, and all other parameters can distinguish them, with AUC changing from 0.551 to 0.615. For T2*-HPs, only Mean and Entropy were reliable for identifying normal and abnormal LFJs with low AUC (0.572, 0.540, respectively).

Conclusions

Histogram analysis of T2/T2* values is feasible for detecting IVD degeneration, but the feasibility of grading LFJ is still controversial. The DI of LFJ is higher than that of IVD under 39 years old, challenging the commonly accepted paradigm of the degenerative process beginning at the IVDs.

腰椎关节突关节（LFJ）和椎间盘退变（IVD）是引起腰痛的常见原因。本研究旨在探讨T2和T2*值直方图分析对LFJ和IVD退行性变分级的可行性，探讨LFJ与IVD在退行性变过程中的相关性。方法对87例患者的420例ivd和840例lfj进行T2WI、T2和T2*成像检查。所有ivd和lfj分别根据Pfirrmann和Weishaupt分级进行分类，并按患者年龄分组。比较各组ivd和lfj的T2 （T2-HPs）和T2* (T2*-HPs)值的直方图参数。结果Pfirrmann评分一致性良好（κ = 0.732）， Weishaupt评分一致性中等（κ = 0.474）。39岁以下患者中，下颞下颌关节退变发生率（DI）高于IVD （χ2 = 16.436, p < 0.001; χ2 = 5.210, p = 0.022）。50 ~ 59岁、60 ~ 69岁组LFJ的DI低于IVD，差异有统计学意义（χ2 = 14.915, p < 0.001; χ2 = 13.174, p < 0.001）。ivd直方图参数的观察者间信度从好到优，ICCs范围为0.825 ~ 0.985，lfj直方图参数的观察者间信度从差到优（0.302 ~ 0.945）。T2- hp和T2*- hp均具有区分正常ivd和异常盘的能力，AUC范围为0.562 ~ 0.824。对于t2 - hp，只有SD和熵不能区分正常（Weishaupt等级0和1）和异常（Weishaupt等级2和3）LFJs，其他参数都可以区分，AUC在0.551到0.615之间变化。对于T2*-HPs，只有Mean和Entropy能够可靠地识别AUC较低的正常和异常LFJs（分别为0.572、0.540）。结论T2/T2*值直方图分析检测IVD退变是可行的，但LFJ分级的可行性仍存在争议。39岁以下LFJ的DI高于IVD，挑战了普遍接受的从IVD开始的退行性过程范式。

{"title":"Evaluation of Lumbar Intervertebral Disc and Facet Joint Degeneration Using Histogram Analysis of T2 and T2* Values","authors":"Xiaoqing Liang, Yitong Li, Bowen Hou, Yan Xiong, John Morelli, Weiyin Vivian Liu, Xiaoming Li","doi":"10.1002/jsp2.70141","DOIUrl":"https://doi.org/10.1002/jsp2.70141","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lumbar facet joint (LFJ) and intervertebral disc (IVD) degeneration are the common causes of low back pain. The aim of this study is to explore the feasibility of histogram analysis of T2 and T2* values on grading LFJ and IVD degeneration and to examine the correlation between the LFJ and IVD in the degenerative process.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>420 IVDs and 840 LFJs of 87 subjects were examined using T2WI, T2 and T2* mapping. All IVDs and LFJs were classified, respectively, according to the Pfirrmann and Weishaupt grade and grouped by patient age. Histogram-derived parameters based on T2 (T2-HPs) and T2* (T2*-HPs) values of IVDs and LFJs were compared among the different groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The interobserver agreement for Pfirrmann grade was good (<i>κ</i> = 0.732), and moderate for Weishaupt grading (<i>κ</i> = 0.474). For patients under 39 years old, the degeneration incidence (DI) of LFJ was higher than IVD (<i>χ</i><sup>2</sup> = 16.436, <i>p</i> < 0.001; <i>χ</i><sup>2</sup> = 5.210, <i>p</i> = 0.022). In the 50–59 and 60–69 years groups, the DI of LFJ was statistically significantly lower than that of IVD (<i>χ</i><sup>2</sup> = 14.915, <i>p</i> < 0.001; <i>χ</i><sup>2</sup> = 13.174, <i>p</i> < 0.001)<i>.</i> The interobserver reliability of histogram parameters for IVDs was good to excellent with ICCs ranging from 0.825 to 0.985, and poor to excellent for LFJs (0.302–0.945). All T2-HPs and T2*-HPs had the ability to distinguish normal IVDs from abnormal discs, with the AUC varying from 0.562 to 0.824. For T2-HPs, only SD and Entropy can not distinguish normal (Weishaupt grades 0 and 1) and abnormal (grades 2 and 3) LFJs, and all other parameters can distinguish them, with AUC changing from 0.551 to 0.615. For T2*-HPs, only Mean and Entropy were reliable for identifying normal and abnormal LFJs with low AUC (0.572, 0.540, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Histogram analysis of T2/T2* values is feasible for detecting IVD degeneration, but the feasibility of grading LFJ is still controversial. The DI of LFJ is higher than that of IVD under 39 years old, challenging the commonly accepted paradigm of the degenerative process beginning at the IVDs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70141","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626157","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

Meta-Analysis of the Application Value of Metagenomic Next-Generation Sequencing Technology in the Diagnosis of Infectious Diseases of the Spine 新一代宏基因组测序技术在脊柱感染性疾病诊断中的应用价值荟萃分析

IF 3.9 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-11-24 DOI: 10.1002/jsp2.70134

Xuejiu Cai, Honglei Yi, Kun Chen, Jianqiang Dai, Jianhua Yi, Bing Tu, Yidan Wang, Jia Li, Jingshen Zhuang

Objective

To evaluate the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) in infectious diseases of the spine (IDS).

Methods

Systematic literature on the application of mNGS in the diagnosis of IDS was retrieved by two independent researchers from databases including Pubmed, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP from the inception to 30 November 2024. Meta-analysis was conducted using Meta-Disc 1.4 and Stata 18.0 software.

Results

The initial search identified 314 articles. After applying predefined inclusion and exclusion criteria, 15 studies were included, encompassing 1236 patients, of which 835 had confirmed IDS. Meta-analysis revealed that the pooled sensitivity and specificity of mNGS for IDS diagnosis were 0.95 (95% CI: 0.88–0.98) and 0.60 (95% CI: 0.48–0.71), respectively. The positive likelihood ratio was 2.3 (95% CI: 1.7–3.2), and the negative likelihood ratio was 0.09 (95% CI: 0.04–0.22). The pooled diagnostic odds ratio was 26 (95% CI: 9–75), with an area under the summary receiver operating characteristic curve of 0.85 (95% CI: 0.82–0.88).

Conclusion

The primary diagnostic value of mNGS lies in its ability to serve as a rapid screening tool for disease exclusion. However, for diagnosing IDS, it is essential to integrate other clinical indicators for a comprehensive assessment to confirm the diagnosis.

目的评价新一代宏基因组测序（mNGS）对脊柱感染性疾病（IDS）的诊断价值。方法由两名独立研究者从Pubmed、中国知网（CNKI）、万方、维普（VIP）等数据库中系统检索自建站至2024年11月30日关于mNGS在IDS诊断中的应用的文献。采用Meta-Disc 1.4和Stata 18.0软件进行meta分析。结果初步检索出314篇文章。应用预定义的纳入和排除标准后，纳入了15项研究，包括1236例患者，其中835例确诊为IDS。meta分析显示，mNGS诊断IDS的总敏感性和特异性分别为0.95 （95% CI: 0.88-0.98）和0.60 （95% CI: 0.48-0.71）。阳性似然比为2.3 (95% CI: 1.7 ~ 3.2)，阴性似然比为0.09 （95% CI: 0.04 ~ 0.22）。合并诊断优势比为26 (95% CI: 9-75)，总受试者工作特征曲线下面积为0.85 （95% CI: 0.82-0.88）。结论mNGS的主要诊断价值在于它能作为一种快速的疾病排除筛查工具。然而，对于诊断IDS，必须结合其他临床指标进行综合评估以确认诊断。

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引用次数: 0

Intracellular Detection of C. acnes and S. aureus in Non-Herniated Human Intervertebral Discs: Implications for Catabolic Signaling Pathways 非突出的人椎间盘细胞内检测痤疮c和金黄色葡萄球菌：对分解代谢信号通路的影响。

IF 3.9 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-11-17 DOI: 10.1002/jsp2.70139

Andrea Nüesch, Exarchos Kanelis, Leonidas G. Alexopoulos, Benjamin Gantenbein, Melissa Lacey, Christine L. Le Maitre

Objective

To investigate whether the presence of bacteria within non-herniated intervertebral discs (IVDs) represents bacterial antigen signals within disc cell boundaries, consistent with in vivo presence and to assess the effects of bacterial exposure on human nucleus pulposus (NP) cells, focusing on immune response pathways and catabolic factor expression.

Methods

Non-herniated IVD tissue was analyzed using immunohistochemistry (n = 79 discs) to detect bacterial presence and its correlation with catabolic factors. Bacterial survival was tested under IVD-like conditions to simulate intradiscal growth potential. Human NP cells were treated with bacterial cell membrane components in both monolayer (n = 3) and 3D cultures (n = 3), with secretome analyzed via Luminex profiling. Co-culture studies investigated bacterial internalization, with NP cells exposed to peptidoglycans or co-cultured with S. aureus or C. acnes at physiologically relevant multiplicities of infection (MOI 0.01, n = 3) to assess intracellular signaling activation.

Results

Immunohistochemical analysis revealed significant correlations between C. acnes intracellular staining and expression of catabolic markers: MMP-3 (p = 3.39 × 10⁻⁴); GSDMD (p = 0.019); and the intracellular receptor: NOD2 (p = 9.6 × 10⁻⁵), implicating these factors in immune surveillance by NP cells. The presence of NOD2 suggests activation of intracellular pathways that contribute to bacterial detection and trigger inflammatory responses. Stimulation of NP cells with peptidoglycan induced a strong catabolic secretome in both 2D and 3D cultures, whilst LPS showed limited effects. Low infectivity of NP cells with C. acnes and S. aureus suppressed VEGF, CXCL10 and CCL5. Effects of peptidoglycan and bacterial co-culture were altered by TLR2/NOD2 inhibition, suggesting receptor-specific but incomplete pathway dependence.

Conclusion

This study identifies key bacterial receptors and signaling pathways in the IVD in response to bacteria, highlighting potential targets for therapeutic intervention in disc-related inflammatory conditions. Our findings support the concept of an active immune role of NP cells in response to bacterial presence, challenging the notion of the disc as a sterile environment.

目的：探讨非突出性椎间盘（IVDs）内细菌的存在是否代表椎间盘细胞边界内的细菌抗原信号，与体内存在一致，并评估细菌暴露对人髓核（NP）细胞的影响，重点关注免疫反应途径和分解代谢因子的表达。方法：采用免疫组化方法对未疝出的IVD组织（79盘）进行细菌检测及其与分解代谢因子的关系。在ivd样条件下测试细菌存活率，以模拟盘内生长潜力。用细菌细胞膜成分对人NP细胞进行单层（n = 3）和三维培养（n = 3）处理，通过Luminex谱分析分泌组。共培养研究研究了细菌内化，将NP细胞暴露于肽聚糖中，或与金黄色葡萄球菌或痤疮球菌在生理相关的感染多重度下共培养（MOI 0.01, n = 3），以评估细胞内信号激活。结果：免疫组化分析显示，痤疮C.胞内染色与分解代谢标志物MMP-3表达有显著相关性（p = 3.39 × 10-4）；GSDMD (p = 0.019)；和细胞内受体NOD2 (p = 9.6 × 10-5)，暗示这些因子参与NP细胞的免疫监视。NOD2的存在表明细胞内通路的激活有助于细菌检测并引发炎症反应。在2D和3D培养中，肽聚糖刺激NP细胞诱导了强烈的分解代谢分泌组，而LPS的作用有限。NP细胞对痤疮C.和金黄色葡萄球菌的低感染性抑制了VEGF、CXCL10和CCL5。TLR2/NOD2抑制可改变肽聚糖和细菌共培养的效果，提示受体特异性但不完全通路依赖。结论：本研究确定了IVD对细菌反应的关键细菌受体和信号通路，突出了椎间盘相关炎症治疗干预的潜在靶点。我们的研究结果支持NP细胞对细菌存在的积极免疫作用的概念，挑战了椎间盘作为无菌环境的概念。

{"title":"Intracellular Detection of C. acnes and S. aureus in Non-Herniated Human Intervertebral Discs: Implications for Catabolic Signaling Pathways","authors":"Andrea Nüesch, Exarchos Kanelis, Leonidas G. Alexopoulos, Benjamin Gantenbein, Melissa Lacey, Christine L. Le Maitre","doi":"10.1002/jsp2.70139","DOIUrl":"10.1002/jsp2.70139","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate whether the presence of bacteria within non-herniated intervertebral discs (IVDs) represents bacterial antigen signals within disc cell boundaries, consistent with in vivo presence and to assess the effects of bacterial exposure on human nucleus pulposus (NP) cells, focusing on immune response pathways and catabolic factor expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Non-herniated IVD tissue was analyzed using immunohistochemistry (<i>n</i> = 79 discs) to detect bacterial presence and its correlation with catabolic factors. Bacterial survival was tested under IVD-like conditions to simulate intradiscal growth potential. Human NP cells were treated with bacterial cell membrane components in both monolayer (<i>n</i> = 3) and 3D cultures (<i>n</i> = 3), with secretome analyzed via Luminex profiling. Co-culture studies investigated bacterial internalization, with NP cells exposed to peptidoglycans or co-cultured with <i>S. aureus</i> or <i>C. acnes</i> at physiologically relevant multiplicities of infection (MOI 0.01, <i>n</i> = 3) to assess intracellular signaling activation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Immunohistochemical analysis revealed significant correlations between <i>C. acnes</i> intracellular staining and expression of catabolic markers: MMP-3 (<i>p</i> = 3.39 × 10<sup>−4</sup>); GSDMD (<i>p</i> = 0.019); and the intracellular receptor: NOD2 (<i>p</i> = 9.6 × 10<sup>−5</sup>), implicating these factors in immune surveillance by NP cells. The presence of NOD2 suggests activation of intracellular pathways that contribute to bacterial detection and trigger inflammatory responses. Stimulation of NP cells with peptidoglycan induced a strong catabolic secretome in both 2D and 3D cultures, whilst LPS showed limited effects. Low infectivity of NP cells with <i>C. acnes</i> and <i>S. aureus</i> suppressed VEGF, CXCL10 and CCL5. Effects of peptidoglycan and bacterial co-culture were altered by TLR2/NOD2 inhibition, suggesting receptor-specific but incomplete pathway dependence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study identifies key bacterial receptors and signaling pathways in the IVD in response to bacteria, highlighting potential targets for therapeutic intervention in disc-related inflammatory conditions. Our findings support the concept of an active immune role of NP cells in response to bacterial presence, challenging the notion of the disc as a sterile environment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12621228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145549143","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}

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