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分析特定损伤相关分子模式相关基因在骨关节炎中的作用,并研究β-淀粉样蛋白与载脂蛋白 E 异构体之间的关系。

Analyzing the Role of Specific Damage-Associated Molecular Patterns-Related Genes in Osteoarthritis and Investigating the Association between β-Amyloid and Apolipoprotein E Isoforms.

机构信息

Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

J Innate Immun. 2024;16(1):501-512. doi: 10.1159/000541542. Epub 2024 Oct 29.

DOI:10.1159/000541542
PMID:39471788
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11521507/
Abstract

INTRODUCTION

Osteoarthritis (OA) is a prevalent chronic joint disorder. It is characterized by an immune response that maintains a low level of inflammation throughout its progression. During OA, cartilage degradation leads to the release of damage-associated molecular patterns (DAMPs), which intensify the inflammatory response. β-Amyloid is a well-recognized DAMP in OA, can interact with APOE isoforms.

METHODS

This study identified DAMPs-related genes in OA using bioinformatics techniques. Additionally, we examined the expression levels of β-amyloid and apolipoprotein E (ApoE) isoforms by enzyme-linked immunosorbent assay.

RESULTS

We identified 10 key genes by machine learning techniques. Immune infiltration analysis revealed upregulation of various immune cell types in OA cartilage, underscoring the critical role of inflammation in OA pathogenesis. In the validation study, elevated serum levels of β-amyloid in knee osteoarthritis (KOA) patients were confirmed, showing positive correlations with ApoE2 and ApoE4. Notably, ApoE3 was identified as an independent protective factor against KOA.

CONCLUSION

In this bioinformatics analysis, we identified the DAMPs-related genes of KOA and explored their potential functions and regulatory networks. The high expression of β-amyloid in KOA was confirmed by experiments, and the correlation between β-amyloid and ApoE2, ApoE4 in KOA was revealed for the first time, this provides a new way to explore the pathogenesis of KOA and to study the therapeutic targets of KOA.

摘要

简介

骨关节炎(OA)是一种普遍存在的慢性关节疾病。它的特征是免疫反应,在整个进展过程中保持低度炎症。在 OA 中,软骨降解导致损伤相关分子模式(DAMPs)的释放,从而加剧炎症反应。β-淀粉样蛋白是 OA 中一种公认的 DAMPs,可与 APOE 异构体相互作用。

方法

本研究使用生物信息学技术鉴定 OA 中的 DAMPs 相关基因。此外,我们通过酶联免疫吸附试验检测了β-淀粉样蛋白和载脂蛋白 E(ApoE)异构体的表达水平。

结果

我们通过机器学习技术确定了 10 个关键基因。免疫浸润分析显示 OA 软骨中各种免疫细胞类型的上调,突出了炎症在 OA 发病机制中的关键作用。在验证研究中,我们证实了膝骨关节炎(KOA)患者血清β-淀粉样蛋白水平升高,并与 ApoE2 和 ApoE4 呈正相关。值得注意的是,ApoE3 被确定为 KOA 的独立保护因素。

结论

在这项生物信息学分析中,我们鉴定了 KOA 的 DAMPs 相关基因,并探讨了它们的潜在功能和调控网络。实验证实了 KOA 中β-淀粉样蛋白的高表达,首次揭示了 KOA 中β-淀粉样蛋白与 ApoE2、ApoE4 的相关性,为探索 KOA 的发病机制和研究 KOA 的治疗靶点提供了新的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb94/11521507/493cab08d271/jin-2024-0016-0001-541542_F06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb94/11521507/7e40bc8f1acf/jin-2024-0016-0001-541542_F01.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb94/11521507/493cab08d271/jin-2024-0016-0001-541542_F06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb94/11521507/7e40bc8f1acf/jin-2024-0016-0001-541542_F01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb94/11521507/9cdebc96d0c3/jin-2024-0016-0001-541542_F02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb94/11521507/4c4302a0d3d8/jin-2024-0016-0001-541542_F03.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb94/11521507/493cab08d271/jin-2024-0016-0001-541542_F06.jpg

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