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

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

Fangling Yuan  1 , Yatian Tang  1 , Feifei Zheng  1 , Qipeng Xie  1
Affiliations

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

Fangling Yuan et al. J Innate Immun. 2024.

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.

Keywords: Apolipoprotein E; Bioinformatics analysis; Damage-associated molecular patterns; Osteoarthritis; β-Amyloid.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1.
Fig. 1.
Technical route of bioinformatics analysis.
Fig. 2.
Fig. 2.
Machine learning for key genes. a LASSO regression. b Random forest. c SVM-RFE. d Correlation analysis of the 10 key genes. e ROC curves of the 10 key genes. SVM-RFE, Support Vector Machine – Recursive Feature Elimination.
Fig. 3.
Fig. 3.
a–j Results of ssGSEA analysis based on reactome database. The following values represent enrichment score, with a score greater than 0 indicating a positive correlation and a score less than 0 indicating a negative correlation.
Fig. 4.
Fig. 4.
ROC curve of β-amyloid.
Fig. 5.
Fig. 5.
a–d Expression of ApoE2, ApoE3, ApoE4, and β-amyloid in different severity of KOA. The severity was graded according to the Kellgren and Lawrence scale.
Fig. 6.
Fig. 6.
a–c Correlation analysis of ApoE2, ApoE3, ApoE4, and β-amyloid.
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Grants and funding

This work was partially supported by grants from the Natural Science Foundation of China (NSFC81601849), Zhejiang Provincial Medicine and Health Technology Project (2019RC217), the Natural Science Foundation of Zhejiang province (LY22H160005).

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