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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。
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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。
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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。
{"title":"Therapeutic Approaches for Enhancing Spinal Fusion in Low Back Pain: A Review With a Focus on the Elderly","authors":"Shuimu Chen,&nbsp;Zhen Li,&nbsp;Sebastian F. Bigdon,&nbsp;Sonja Häckel,&nbsp;Christoph E. Albers,&nbsp;Benjamin Gantenbein","doi":"10.1002/jsp2.70136","DOIUrl":"10.1002/jsp2.70136","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12606028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512873","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
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 Ift88flox /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,&nbsp;Shuqing Chen,&nbsp;Fushuai Peng,&nbsp;Yukun Du,&nbsp;Jianyi Li,&nbsp;Yuanyuan Fan,&nbsp;Zichen Cui,&nbsp;Guanghui Gu,&nbsp;Han Zhang,&nbsp;Xingzhi Jing,&nbsp;Jun Dong,&nbsp;Tao Li,&nbsp;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> &lt; 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}
引用次数: 0
The Impact of the Ovine Annular Lesion Model on IVD Pathobiology and Utility of the Ovine Spinal Model in Patho-Anatomical Studies: A Historical Perspective 羊环形病变模型对IVD病理生物学的影响及羊脊柱模型在病理解剖研究中的应用：一个历史的视角。
IF 3.9 3区 医学 Q1 ORTHOPEDICS
JOR Spine
Pub Date : 2025-11-04 DOI: 10.1002/jsp2.70128
O. Osti, C. B. Little, J. Melrose

This review documents the impact of the Osti ovine annular lesion model of intervertebral disc (IVD) degeneration on the elucidation of degenerative changes in the ovine IVD also seen in human IVD degeneration (IVDD). The degenerative pathology knowledge base generated by the ovine model over the last 35 years has provided invaluable insights into degenerative events occurring in the human IVD. Changes in para-discal structures as a consequence of IVDD, in vertebral bone adjacent to the lesion site, cartilaginous endplates and spinal motion segment facet joints, and in the longitudinal ligaments and paraspinal muscles also affect spinal stability and flexibility. All of these spinal structures are richly innervated, and disturbance of their normal architecture due to IVDD also contributes to the generation of low back pain. Like human IVDD, when the ovine IVD is mechanically destabilized by the introduction of a controlled annular lesion, release of proteases is elevated, degradation of structural ECM components occurs, leading to IVDD and biomechanical impairment. When space-filling aggrecan is degraded in the IVD, a drop in internal hydrostatic pressure occurs, and the IVD becomes susceptible to an ingrowth of blood vessels and mechanosensitive nociceptors resulting in enhanced generation of low back pain by the biomechanically incompetent IVD. The ovine model is thus very useful to evaluate compounds or procedures that slow IVDD and, in some cases, promote regenerative processes. The large size of the ovine IVD allows the use of inter-disciplinary longitudinal approaches in the analysis of progressive changes in the degenerate IVD of relevance to the human IVD.

Clinical Significance

The ovine annular lesion model of IVDD displays similar pathological features to those displayed by the degenerate human IVD, making it an appropriate model for the evaluation of IVD reparative procedures. Furthermore, the resident ovine IVD cell populations are similar to those seen in the human IVD, with a disappearance of notochordal cells occurring in adolescence. This is not the case in many other popular animal (murine, rat, porcine, lapine, and non-chondrodystrophic canine) models of IVDD. The persistence of notochordal cells into adulthood in these breeds questions how translatable findings generated in these models are to the human IVD. The ovine model is thus relevant to the development of strategies exploring novel strategies in IVD repair and the recovery of normal IVD structure and function. Mesenchymal stem cells have impressive IVD repair and recovery of structure and function properties, showing promise in the treatment of the degenerate human IVD.

本文综述了Osti羊椎间盘（IVD）变性环形病变模型对阐明羊椎间盘（IVD）退行性改变的影响，也在人类椎间盘（IVD）变性（IVDD）中看到。在过去的35年里，由羊模型产生的退行性病理知识库为人类IVD中发生的退行性事件提供了宝贵的见解。IVDD导致的椎间盘旁结构、病变部位附近的椎体骨、软骨终板和脊柱运动节段小关节、纵向韧带和棘旁肌肉的变化也会影响脊柱的稳定性和柔韧性。所有这些脊柱结构都有丰富的神经支配，IVDD对其正常结构的干扰也有助于腰痛的产生。与人类IVDD一样，当羊IVD通过引入可控的环形病变而在机械上不稳定时，蛋白酶的释放会升高，结构性ECM成分会发生降解，从而导致IVDD和生物力学损伤。当填充空间的聚集蛋白在IVD中降解时，内部静水压力下降，IVD容易受到血管和机械敏感伤害感受器的生长影响，导致生物力学功能不佳的IVD产生的腰痛增加。因此，羊模型对于评估减缓IVDD的化合物或程序非常有用，在某些情况下，可以促进再生过程。绵羊IVD的大尺寸允许使用跨学科的纵向方法来分析与人类IVD相关的退化IVD的进行性变化。临床意义：绵羊IVDD环形病变模型与人类IVD退行性病变的病理特征相似，是评价IVD修复手术的合适模型。此外，常驻的绵羊IVD细胞群与在人类IVD中看到的相似，在青春期出现脊索细胞的消失。在许多其他流行的动物（小鼠、大鼠、猪、松鸡和非软骨营养不良犬）的IVDD模型中，情况并非如此。这些品种的脊索细胞在成年期的持续存在，质疑这些模型中产生的发现对人类IVD的可翻译性。因此，绵羊模型与探索IVD修复和恢复正常IVD结构和功能的新策略的发展有关。间充质干细胞具有令人印象深刻的IVD修复和恢复结构和功能特性，在治疗退行性人类IVD方面显示出前景。
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引用次数: 0
Beyond the Curve: The Muscle-Specific Asymmetries of Adolescent Idiopathic Scoliosis 曲线之外：青少年特发性脊柱侧凸的肌肉特异性不对称。
IF 3.9 3区 医学 Q1 ORTHOPEDICS
JOR Spine
Pub Date : 2025-11-04 DOI: 10.1002/jsp2.70129
Phoebe Duncombe, Taylor Dick, Phoebe T. T. Ng, Maree T. Izatt, Robert D. Labrom, Kylie Tucker
<div> <section> <h3> Background</h3> <p>Adolescent idiopathic scoliosis (AIS) describes an asymmetrical formation of the spine that develops rapidly during adolescence. It is well known that the forces applied to bones, such as from paraspinal muscles, are substantial moderators of growth and adaptation. Despite the intimate relationship between the paraspinal muscles and the spine, very little is known about these muscles, particularly during adolescence when there is the greatest risk of the development and progression of AIS. Here, we aimed to quantify paraspinal muscle volume, intramuscular fat, and fat-free muscle asymmetry in female adolescents with AIS and a healthy adolescent control cohort.</p> </section> <section> <h3> Methods</h3> <p>Twenty-nine female adolescents with primary-right-thoracic scoliosis (range: Cobb angle mean [SD]: 39 [15]°; age mean [SD]: 13.8 [1.5] years) and 19 age-matched female control participants without scoliosis (age mean [SD]: 13.1 [1.8] years). Participants underwent T1-weighted and coronal mDixon magnetic resonance image scans. An Asymmetry<sub><i>index</i></sub> of muscle volume, intramuscular-fat, and fat-free muscle were determined for five paraspinal muscles across 11 vertebral levels (T4-L4/5) (Asymmetry<sub><i>index</i></sub> = Ln [right-side/left-side]).</p> </section> <section> <h3> Results</h3> <p>AIS participants have greater asymmetry in paraspinal muscle volume, intramuscular fat, and fat-free muscle compared to controls (<i>p</i> < 0.05, linear mixed effects analysis). Across numerous vertebral levels adjacent to the primary thoracic curve apex in AIS, multifidus volume and multifidus, longissimus, and spinalis intramuscular fat asymmetries were greater in AIS (13%–57% larger on the left side) than in the control group (1%–20%), <i>p</i> < 0.05. In the lumbar spine, multifidus volume and multifidus, longissimus, and psoas intramuscular fat were greater on the right side of the lumbar curve in AIS (18%–54%) than in controls (1%–14%), <i>p</i> < 0.05. Scoliosis curve severity was moderately correlated with asymmetries in muscle volume, intramuscular fat, and fat-free muscle (range: <i>R</i> = 0.40–0.64, <i>p</i> < 0.05).</p> </section> <section> <h3> Conclusions</h3> <p>These findings provide evidence that asymmetries in paraspinal muscle size and composition exist along the length of the scoliotic spine. The asymmetries are associated with curve severity; therefore, supporting the need to further consider muscle in the pathogenesis of AIS.</p> </section> </div
背景：青少年特发性脊柱侧凸（AIS）描述了一种在青春期迅速发展的脊柱不对称形成。众所周知，施加在骨骼上的力，如来自棘旁肌肉的力，是生长和适应的重要调节因子。尽管棘旁肌和脊柱之间有密切的关系，但对这些肌肉知之甚少，特别是在AIS发展和进展的风险最大的青少年时期。在这里，我们旨在量化患有AIS的女性青少年和健康青少年对照队列的棘旁肌肉体积、肌内脂肪和无脂肪肌肉不对称。方法：29名患有原发性右胸侧凸的女性青少年（范围：Cobb角平均值[SD]: 39[15]°；年龄平均值[SD]: 13.8[1.5]岁）和19名年龄匹配的无侧凸的女性对照组（年龄平均值[SD]: 13.1[1.8]岁）。参与者接受了t1加权和冠状mDixon磁共振成像扫描。测定横跨11个椎体节段（T4-L4/5）的5块棘旁肌的肌肉体积、肌内脂肪和无脂肪肌肉的不对称指数（不对称指数= Ln[右侧/左侧]）。结果：与对照组相比，AIS参与者在棘旁肌肉体积、肌内脂肪和无脂肪肌肉方面具有更大的不对称性（p p p R = 0.40-0.64, p）。结论：这些发现提供了证据，表明沿脊柱侧凸长度存在棘旁肌肉大小和组成的不对称性。不对称性与曲线的严重程度有关；因此，支持在AIS发病机制中进一步考虑肌肉的必要性。
{"title":"Beyond the Curve: The Muscle-Specific Asymmetries of Adolescent Idiopathic Scoliosis","authors":"Phoebe Duncombe,&nbsp;Taylor Dick,&nbsp;Phoebe T. T. Ng,&nbsp;Maree T. Izatt,&nbsp;Robert D. Labrom,&nbsp;Kylie Tucker","doi":"10.1002/jsp2.70129","DOIUrl":"10.1002/jsp2.70129","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;Adolescent idiopathic scoliosis (AIS) describes an asymmetrical formation of the spine that develops rapidly during adolescence. It is well known that the forces applied to bones, such as from paraspinal muscles, are substantial moderators of growth and adaptation. Despite the intimate relationship between the paraspinal muscles and the spine, very little is known about these muscles, particularly during adolescence when there is the greatest risk of the development and progression of AIS. Here, we aimed to quantify paraspinal muscle volume, intramuscular fat, and fat-free muscle asymmetry in female adolescents with AIS and a healthy adolescent control cohort.&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;Twenty-nine female adolescents with primary-right-thoracic scoliosis (range: Cobb angle mean [SD]: 39 [15]°; age mean [SD]: 13.8 [1.5] years) and 19 age-matched female control participants without scoliosis (age mean [SD]: 13.1 [1.8] years). Participants underwent T1-weighted and coronal mDixon magnetic resonance image scans. An Asymmetry&lt;sub&gt;&lt;i&gt;index&lt;/i&gt;&lt;/sub&gt; of muscle volume, intramuscular-fat, and fat-free muscle were determined for five paraspinal muscles across 11 vertebral levels (T4-L4/5) (Asymmetry&lt;sub&gt;&lt;i&gt;index&lt;/i&gt;&lt;/sub&gt; = Ln [right-side/left-side]).&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;AIS participants have greater asymmetry in paraspinal muscle volume, intramuscular fat, and fat-free muscle compared to controls (&lt;i&gt;p&lt;/i&gt; &lt; 0.05, linear mixed effects analysis). Across numerous vertebral levels adjacent to the primary thoracic curve apex in AIS, multifidus volume and multifidus, longissimus, and spinalis intramuscular fat asymmetries were greater in AIS (13%–57% larger on the left side) than in the control group (1%–20%), &lt;i&gt;p&lt;/i&gt; &lt; 0.05. In the lumbar spine, multifidus volume and multifidus, longissimus, and psoas intramuscular fat were greater on the right side of the lumbar curve in AIS (18%–54%) than in controls (1%–14%), &lt;i&gt;p&lt;/i&gt; &lt; 0.05. Scoliosis curve severity was moderately correlated with asymmetries in muscle volume, intramuscular fat, and fat-free muscle (range: &lt;i&gt;R&lt;/i&gt; = 0.40–0.64, &lt;i&gt;p&lt;/i&gt; &lt; 0.05).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;These findings provide evidence that asymmetries in paraspinal muscle size and composition exist along the length of the scoliotic spine. The asymmetries are associated with curve severity; therefore, supporting the need to further consider muscle in the pathogenesis of AIS.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 &lt;/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/PMC12585792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451478","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
Correction to “Patient-Reported Outcomes Among an Observational Cohort of Individuals With Chronic Low Back Pain” 更正“慢性腰痛患者报告的观察性队列结果”。
IF 3.9 3区 医学 Q1 ORTHOPEDICS
JOR Spine
Pub Date : 2025-10-27 DOI: 10.1002/jsp2.70132

C. M. Greco, N. E. Dodds, A. M. Acevedo, et al., “Patient-Reported Outcomes Among an Observational Cohort of Individuals With Chronic Low Back Pain,” JOR Spine 8, no. 3 (2025): e70097, https://doi.org/10.1002/jsp2.70097.

The originally published Table 2 contains an error. The percentages within the “Risk stratification” row were incorrect. The corrected table is provided below.

An error occurred on page 7 in Section 4.2, “Pain-Related Psychosocial Factors”, sentences 6 and 7. The corrected text is as follows:

Participants endorsed a high level of ignoring or distracting from pain on the MAIA-2 Not-Distracting Scale. On the STarT Back screen, which combines problematic psychosocial factors with disability perceptions to yield a risk score for chronicity, 21 percent of participants were categorized as high risk.

We apologize for these errors.

[更正文章DOI: 10.1002/jsp2.70097.]。
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引用次数: 0
Lactate Metabolism in Intervertebral Disc Degeneration: Unveiling Novel Mechanisms Through Bioinformatics 椎间盘退变中的乳酸代谢：通过生物信息学揭示新的机制
IF 3.9 3区 医学 Q1 ORTHOPEDICS
JOR Spine
Pub Date : 2025-10-20 DOI: 10.1002/jsp2.70126
Haiyan Sun, Mingwei He, Jinlei Pang, Xiangfei Guo, Yansong Huo, Jun Ma

Background

Intervertebral disc degeneration (IDD) is a widespread issue associated with chronic lumbar pain and disability. This study aimed to identify lactate metabolism-related genes in IDD and elucidate their mechanistic roles in disease progression.

Methods

IDD datasets were analyzed using R packages GEOquery, sva, and limma for data retrieval, batch correction, and normalization. Differential gene expression analysis identified significant genes between IDD and control groups, from which lactate metabolism-related differentially expressed genes (LMRDEGs) were derived. Relationships among the LMRDEGs were assessed using Spearman's correlation analysis, and functional enrichment was conducted using ClusterProfiler. Gene set enrichment analysis identified biological processes associated with IDD. Diagnostic models were assessed using receiver operating characteristic (ROC) curve. Immune cell infiltration and correlations with core genes were analyzed via the CIBERSORT algorithm. Regulatory networks were constructed, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to validate the expression of hub LMRDEGs in IDD.

Results

A total of 1325 differentially expressed genes were identified, yielding seven LMRDEGs: TGFβ2, GSR, MB, MMP2, SLC16A7, PER2, and STAT3, which are enriched in blood circulation regulation and hypoxic response, as well as pathways like AGE–RAGE signaling in diabetic complications. ROC analysis indicated potential hub genes (MMP2, MB, TGFβ2, and PER2), while immune infiltration analysis uncovered significant variations in immune cell distribution. RT-qPCR confirmed MMP2, MB, and SLC16A7 as molecular indicators reflecting lactate metabolism abnormalities in IDD.

Conclusion

This study clarifies how lactate metabolism contributes to IDD through molecular mechanisms and its interplay with immunological features, providing a theoretical basis for understanding the early pathogenesis of IDD.

背景椎间盘退变（IDD）是一种与慢性腰痛和残疾相关的普遍问题。本研究旨在鉴定IDD中乳酸代谢相关基因，并阐明其在疾病进展中的机制作用。方法采用GEOquery、sva和limma等R软件包对IDD数据集进行检索、批量校正和归一化处理。差异基因表达分析发现了IDD组与对照组之间的显著基因，由此衍生出乳酸代谢相关差异表达基因（LMRDEGs）。使用Spearman相关分析评估lmrdeg之间的关系，并使用ClusterProfiler进行功能富集。基因集富集分析确定了与IDD相关的生物过程。采用受试者工作特征（ROC）曲线对诊断模型进行评估。通过CIBERSORT算法分析免疫细胞浸润及其与核心基因的相关性。构建调控网络，利用逆转录定量聚合酶链反应（RT-qPCR）验证hub LMRDEGs在IDD中的表达。结果共鉴定出1325个差异表达基因，得到tgf - β2、GSR、MB、MMP2、SLC16A7、PER2和STAT3 7个lmrdeg，这些基因丰富于糖尿病并发症的血液循环调节和缺氧反应，以及AGE-RAGE信号通路。ROC分析发现了潜在的枢纽基因（MMP2、MB、tgf - β2和PER2），而免疫浸润分析发现了免疫细胞分布的显著变化。RT-qPCR证实MMP2、MB、SLC16A7是反映IDD乳酸代谢异常的分子指标。结论本研究阐明了乳酸代谢对IDD的分子机制及其与免疫特性的相互作用，为了解IDD的早期发病机制提供了理论基础。
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引用次数: 0
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