JOR Spine最新文献_第2页

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。

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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}

引用次数: 0

Therapeutic Approaches for Enhancing Spinal Fusion in Low Back Pain: A Review With a Focus on the Elderly 加强腰痛脊柱融合的治疗方法：以老年人为重点的综述。

IF 3.9 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-11-12 DOI: 10.1002/jsp2.70136

Shuimu Chen, Zhen Li, Sebastian F. Bigdon, Sonja Häckel, Christoph E. Albers, Benjamin Gantenbein

Background

Low back pain (LBP) is a prevalent cause of disability worldwide, particularly among the elderly, with degenerative spinal conditions often necessitating surgical intervention. Spinal fusion remains a definitive treatment for patients unresponsive to conservative therapies, yet its success is challenged by age-related factors such as osteoporosis, diminished stem cell function, and vascular insufficiency.

Methods

This review examines current and emerging strategies to improve spinal fusion outcomes for elderly patients by analyzing advances in biomaterials, growth factor delivery systems, cell-based regenerative therapies, surgical innovations, and some novel approaches.

Results

Advances in biomaterials, including bioactive scaffolds, 3D-printed constructs, and hybrid grafts, provide structural and biological support for bone formation. Growth factor delivery systems, particularly controlled-release formulations of bone morphogenetic proteins (BMPs) and vascular endothelial growth factor (VEGF), improve osteoinduction while mitigating adverse effects. Cell-based regenerative therapies utilizing mesenchymal stromal cells (MSCs) and extracellular vesicles (EVs) offer promising osteogenic and immunomodulatory potential. Furthermore, minimally invasive surgical techniques and robotic-assisted procedures provide additional options for enhancing spinal fusion in elderly patients. Novel approaches targeting cellular senescence, epigenetic modulation, and mitochondrial dysfunction are emerging to counteract age-related impairments in bone formation.

Conclusion

Despite significant advancements, challenges such as optimizing biomaterial integration, mitigating inflammatory responses, and ensuring long-term stability remain. Future research should leverage precision medicine, artificial intelligence, and nanotechnology to enable patient-specific fusion strategies. A multidisciplinary approach will be essential to improve spinal fusion outcomes for aging populations.

背景：腰痛（LBP）是世界范围内残疾的普遍原因，特别是在老年人中，脊柱退行性疾病通常需要手术干预。对于对保守疗法无反应的患者，脊柱融合术仍然是一种确定的治疗方法，但其成功与否受到年龄相关因素的挑战，如骨质疏松症、干细胞功能减弱和血管功能不全。方法：本综述通过分析生物材料、生长因子传递系统、细胞再生疗法、外科创新和一些新方法的进展，研究了当前和新兴的改善老年患者脊柱融合结果的策略。结果：生物材料的进展，包括生物活性支架、3d打印构建体和杂交移植物，为骨形成提供了结构和生物支持。生长因子输送系统，特别是骨形态发生蛋白（bmp）和血管内皮生长因子（VEGF）的控释制剂，在减轻不良反应的同时改善骨诱导。利用间充质基质细胞（MSCs）和细胞外囊泡（EVs）的细胞再生疗法具有成骨和免疫调节潜力。此外，微创手术技术和机器人辅助手术为增强老年患者脊柱融合提供了额外的选择。针对细胞衰老、表观遗传调节和线粒体功能障碍的新方法正在出现，以抵消骨形成中与年龄相关的损伤。结论：尽管取得了重大进展，但优化生物材料整合、减轻炎症反应和确保长期稳定性等挑战仍然存在。未来的研究应该利用精准医疗、人工智能和纳米技术来实现针对患者的融合策略。多学科的方法将是必要的，以提高脊柱融合的结果为老年人。

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引用次数: 0

Lovastatin-Loaded Nanoparticles in a Thermosensitive Chitosan Hydrogel as a Sustained Release System for Treating Intervertebral Disc Degeneration: In Vitro Cell Culture Study and In Vivo Evaluation Using a Needle-Puncture Induced Degeneration Model in Rat Caudal Discs 热敏壳聚糖水凝胶中负载洛伐他汀纳米颗粒作为缓释系统治疗椎间盘退变：体外细胞培养研究和针刺诱导大鼠尾盘退变模型的体内评价

IF 3.9 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-11-10 DOI: 10.1002/jsp2.70135

Chih-Wei Chen, Yung-Hsin Cheng, Kai-Chiang Yang, Chuan-Ching Huang, Ming-Hsiao Hu, Yuan-Hui Sun, Jaw-Lin Wang, Shu-Hua Yang

Background

Sustained release of therapeutic factors, such as lovastatin, is theoretically more beneficial than a single injection in promoting anabolic stimulation to nucleus pulposus cells/tissues. This study aimed to develop lovastatin-loaded nanoparticles (LVS-NPs) incorporated into thermosensitive chitosan/gelatin/glycerophosphate (C/G/GP) hydrogel for the treatment of intervertebral disc (IVD) degeneration.

Methods

LVS-NPs were prepared using an oil-in-water emulsion evaporation method, followed by characterization and drug encapsulation efficiency. LVS-NPs were then incorporated into C/G/GP hydrogel for controlled drug release, with subsequent in vitro and in vivo evaluations.

Results

LVS-NPs showed a round shape with a mid-range polydispersity index, which shall benefit lovastatin release. Rheological study showed incorporation of LVS-NPs into hydrogel does not change thermal gelation property. Drug release tests demonstrated that lovastatin was released steadily from the hydrogel containing LVS-NPs over 7 days. The LVS-NPs-containing hydrogel demonstrated good biocompatibility and low cytotoxicity in the in vitro studies including WST-8 assay, LDH assay, TUNEL test and Western blot. Analysis of hydrogels containing LVS-NPs on human nucleus pulposus cells revealed enhanced production of aggrecan and Type II collagen without inducing apoptosis, though higher concentrations or longer treatment durations may be required to achieve effects comparable to those of 5 μM lovastatin. In the animal study, various treatment regimens were applied to a rat caudal disc model mimicking early-stage IVD degeneration. Despite lovastatin or LVS-NPs in hydrogel, significant decreases in disc height index and extensive degeneration observed through MRI and histological staining indicated a complete loss of nucleus pulposus tissue in all hydrogel-treated groups, likely due to mechanical compression from the injected hydrogel within the confined space of the annulus fibrosus, which needs further investigation.

Conclusions

LVS-NPs demonstrated sustained release of lovastatin and extended stimulatory effects on human nucleus pulposus cells in vitro. However, further research is needed to optimize the hydrogel volume and its ratio to intradiscal space and increase lovastatin concentration within LVS-NPs to achieve optimal therapeutic outcomes while minimizing mechanical compression to surrounding tissues.

背景：在促进髓核细胞/组织的合成代谢刺激方面，持续释放治疗因子，如洛伐他汀，理论上比单次注射更有益。本研究旨在将洛伐他汀负载纳米颗粒（LVS-NPs）掺入热敏壳聚糖/明胶/甘油磷酸（C/G/GP）水凝胶中，用于治疗椎间盘（IVD）退变。方法：采用油包水乳状液蒸发法制备LVS-NPs，并对其进行表征和药物包封效率测定。然后将LVS-NPs掺入C/G/GP水凝胶中控释，并进行体外和体内评价。结果：LVS-NPs呈圆形，多分散指数中等，有利于洛伐他汀释放。流变学研究表明，LVS-NPs掺入水凝胶不会改变水凝胶的热凝胶性质。药物释放试验表明，洛伐他汀在7天内从含有LVS-NPs的水凝胶中稳定释放。体外WST-8、LDH、TUNEL、Western blot等实验结果表明，lvs - nps水凝胶具有良好的生物相容性和较低的细胞毒性。对含有LVS-NPs的水凝胶对人髓核细胞的分析显示，尽管可能需要更高的浓度或更长的治疗时间才能达到与5 μM洛瓦斯他汀相当的效果，但在不诱导细胞凋亡的情况下，LVS-NPs增强了聚集蛋白和II型胶原的产生。在动物实验中，对模拟早期IVD退变的大鼠尾盘模型应用了不同的治疗方案。尽管水凝胶中有洛伐他汀或LVS-NPs，但通过MRI和组织学染色观察到的椎间盘高度指数显著下降和广泛退变表明，在所有水凝胶处理组中，髓核组织完全丢失，可能是由于注射的水凝胶在纤维环受限空间内的机械压迫，这需要进一步研究。结论：LVS-NPs体外对人髓核细胞具有洛伐他汀缓释作用和延长的刺激作用。然而，进一步的研究需要优化水凝胶体积及其与椎间盘间隙的比例，增加LVS-NPs内洛伐他汀的浓度，以达到最佳的治疗效果，同时最大限度地减少对周围组织的机械压迫。

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引用次数: 0

PIEZO1-Primary Cilia Axis Mediates Compressive Stress-Induced Growth Plate Degeneration and Ossification in Adolescent Idiopathic Scoliosis piezo1 -初级纤毛轴介导压缩应力诱导的生长板变性和骨化在青少年特发性脊柱侧凸。

IF 3.9 3区医学 Q1 ORTHOPEDICS

JOR Spine

Pub Date : 2025-11-04 DOI: 10.1002/jsp2.70133

Fei Chen, Shuqing Chen, Fushuai Peng, Yukun Du, Jianyi Li, Yuanyuan Fan, Zichen Cui, Guanghui Gu, Han Zhang, Xingzhi Jing, Jun Dong, Tao Li, Yongming Xi

Background

Adolescent idiopathic scoliosis (AIS) is linked to mechanical stress-induced growth plate dysfunction. PIEZO1 (mechanosensitive ion channel) mediates chondrocyte apoptosis via calcium, and primary cilia (mechanosensory organelles) regulate cartilage matrix synthesis, but their interplay in stress-induced growth plate degeneration/ossification remains unclear; this study explored the PIEZO1-primary cilia axis's role.

Methods

Conditional IFT88 knockout (IFT88-cKO) mice were generated via Col2a1-CreERT and Ift88^{flox /}^flox crosses (tamoxifen-induced). 8-week-old C57BL/6J mice were divided into control, wild-type caudal compression (CC, 10 kPa), and IFT88-CKO CC groups (samples at 8 weeks, MRI at 4 weeks). Primary growth plate chondrocytes from 5-day-old C57BL/6J mice were cultured, stressed (self-developed device, 100 kPa), or treated with Yoda1 (PIEZO1 agonist)/chloral hydrate (cilia disruptor)/siRNA (PIEZO1/IFT88 knockdown). Detection included Western blot, RT-qPCR, immunofluorescence, immunohistochemistry, ARS/ALP/ABS/HE/Safranine O staining, and transcriptome sequencing.

Results

PIEZO1 co-localized with primary cilia (ac-α-Tubulin labeled) in chondrocytes; chloral hydrate reduced cil-ia-positive cells (97.2% → 16.6%, p < 0.001). Stress upregulated PIEZO1, decreased COL2A1 (cartilage marker), increased RUNX2 (osteogenic marker), and enhanced ALP/ARS staining. Transcriptome identified 11,534 differ-entially expressed genes (e.g., upregulated PIEZO1/IFT88, downregulated ACAN). SiPIEZO1 reduced IFT88 (non-stress), while siIFT88 feedback-upregulated PIEZO1 (stress). Yoda1 induced cartilage degeneration, which was reversed by siIFT88/chloral hydrate. In vivo, CC increased disc degeneration score (2 → 12), while IFT88-cKO reduced it to 8 and attenuated COL2A1 downregulation/RUNX2 upregulation.

Conclusion

The PIEZO1-primary cilia axis mediates stress-induced growth plate degeneration/ossification: stress upregulates PIEZO1, which relies on primary cilia to promote chondrocyte apoptosis and abnormal ossification; cilia disruption alleviates these effects. This provides insights into AIS pathogenesis and identifies PIEZO1/primary cilia as therapeutic targets.

背景：青少年特发性脊柱侧凸（AIS）与机械应力诱导的生长板功能障碍有关。PIEZO1（机械敏感离子通道）通过钙介导软骨细胞凋亡，初级纤毛（机械感觉细胞器）调节软骨基质合成，但它们在应力诱导的生长板变性/骨化中的相互作用尚不清楚；本研究探讨了piezo1 -初级纤毛轴的作用。方法：通过col21a - creert和IFT88 flox / flox杂交（他莫昔芬诱导）产生IFT88条件敲除（IFT88- cko）小鼠。将8周龄C57BL/6J小鼠分为对照组、野生型尾侧压迫组（CC, 10 kPa）和IFT88-CKO CC组（8周取样，4周MRI）。对5日龄C57BL/6J小鼠的原代生长板软骨细胞进行培养、应激（自行研制的装置，100 kPa）或Yoda1 （PIEZO1激动剂）/水合氯醛（纤毛干扰物）/siRNA （PIEZO1/IFT88敲低物）处理。检测方法包括Western blot、RT-qPCR、免疫荧光、免疫组织化学、ARS/ALP/ABS/HE/Safranine O染色、转录组测序。结果：PIEZO1在软骨细胞中与原生纤毛共定位（ac-α-微管蛋白标记）；结论：PIEZO1原毛轴介导应力诱导的生长板退变/骨化，应激可上调PIEZO1，其依赖原毛促进软骨细胞凋亡和异常骨化，而纤毛破坏可减轻这种作用。这提供了对AIS发病机制的深入了解，并确定了PIEZO1/初级纤毛作为治疗靶点。

{"title":"PIEZO1-Primary Cilia Axis Mediates Compressive Stress-Induced Growth Plate Degeneration and Ossification in Adolescent Idiopathic Scoliosis","authors":"Fei Chen, Shuqing Chen, Fushuai Peng, Yukun Du, Jianyi Li, Yuanyuan Fan, Zichen Cui, Guanghui Gu, Han Zhang, Xingzhi Jing, Jun Dong, Tao Li, Yongming Xi","doi":"10.1002/jsp2.70133","DOIUrl":"10.1002/jsp2.70133","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Adolescent idiopathic scoliosis (AIS) is linked to mechanical stress-induced growth plate dysfunction. PIEZO1 (mechanosensitive ion channel) mediates chondrocyte apoptosis via calcium, and primary cilia (mechanosensory organelles) regulate cartilage matrix synthesis, but their interplay in stress-induced growth plate degeneration/ossification remains unclear; this study explored the PIEZO1-primary cilia axis's role.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Conditional IFT88 knockout (IFT88-cKO) mice were generated via <i>Col2a1</i>-<i>CreERT</i> and <i>Ift88</i><sup><i>flox /</i></sup><sup><i>flox</i></sup> crosses (tamoxifen-induced). 8-week-old C57BL/6J mice were divided into control, wild-type caudal compression (CC, 10 kPa), and IFT88-CKO CC groups (samples at 8 weeks, MRI at 4 weeks). Primary growth plate chondrocytes from 5-day-old C57BL/6J mice were cultured, stressed (self-developed device, 100 kPa), or treated with Yoda1 (PIEZO1 agonist)/chloral hydrate (cilia disruptor)/siRNA (PIEZO1/IFT88 knockdown). Detection included Western blot, RT-qPCR, immunofluorescence, immunohistochemistry, ARS/ALP/ABS/HE/Safranine O staining, and transcriptome sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PIEZO1 co-localized with primary cilia (ac-α-Tubulin labeled) in chondrocytes; chloral hydrate reduced cil-ia-positive cells (97.2% → 16.6%, <i>p</i> < 0.001). Stress upregulated PIEZO1, decreased COL2A1 (cartilage marker), increased RUNX2 (osteogenic marker), and enhanced ALP/ARS staining. Transcriptome identified 11,534 differ-entially expressed genes (e.g., upregulated PIEZO1/IFT88, downregulated ACAN). SiPIEZO1 reduced IFT88 (non-stress), while siIFT88 feedback-upregulated PIEZO1 (stress). Yoda1 induced cartilage degeneration, which was reversed by siIFT88/chloral hydrate. In vivo, CC increased disc degeneration score (2 → 12), while IFT88-cKO reduced it to 8 and attenuated COL2A1 downregulation/RUNX2 upregulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The PIEZO1-primary cilia axis mediates stress-induced growth plate degeneration/ossification: stress upregulates PIEZO1, which relies on primary cilia to promote chondrocyte apoptosis and abnormal ossification; cilia disruption alleviates these effects. This provides insights into AIS pathogenesis and identifies PIEZO1/primary cilia as therapeutic targets.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12585761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451493","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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