Lactate Metabolism in Intervertebral Disc Degeneration: Unveiling Novel Mechanisms Through Bioinformatics

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

{"title":"Lactate Metabolism in Intervertebral Disc Degeneration: Unveiling Novel Mechanisms Through Bioinformatics","authors":"Haiyan Sun, Mingwei He, Jinlei Pang, Xiangfei Guo, Yansong Huo, Jun Ma","doi":"10.1002/jsp2.70126","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>A total of 1325 differentially expressed genes were identified, yielding seven LMRDEGs: <i>TGFβ2</i>, <i>GSR</i>, <i>MB</i>, <i>MMP2</i>, <i>SLC16A7</i>, <i>PER2</i>, and <i>STAT3</i>, 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 (<i>MMP2, MB, TGFβ2</i>, and <i>PER2</i>), while immune infiltration analysis uncovered significant variations in immune cell distribution. RT-qPCR confirmed <i>MMP2</i>, <i>MB</i>, and <i>SLC16A7</i> as molecular indicators reflecting lactate metabolism abnormalities in IDD.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 4","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70126","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JOR Spine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jsp2.70126","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ORTHOPEDICS","Score":null,"Total":0}

引用次数: 0

Abstract

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.

Abstract Image

查看原文本刊更多论文

椎间盘退变中的乳酸代谢：通过生物信息学揭示新的机制

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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊