Supplementary Material for: Analyzing the Role of Specific DAMPs-Related Genes in Osteoarthritis and Investigating the Association Between β-Amyloid and ApoE Isoforms

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 ApoE isoforms by ELISA.
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 βAmyloid 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.

引言：骨关节炎（Osteoarthritis, OA）是一种高发的慢性关节疾病，其特征为病程中持续维持低水平炎症的免疫应答。在骨关节炎进程中，软骨降解会释放损伤相关分子模式（damage-associated molecular patterns, DAMPs），进而加剧炎症反应。β淀粉样蛋白是骨关节炎中已被广泛确认的DAMPs，可与载脂蛋白E（APOE）异构体相互作用。
方法：本研究通过生物信息学技术筛选骨关节炎中与DAMPs相关的基因。此外，我们采用酶联免疫吸附测定（ELISA）检测了β淀粉样蛋白与载脂蛋白E异构体的表达水平。
结果：我们通过机器学习技术筛选出10个关键基因。免疫浸润分析显示，骨关节炎软骨中多种免疫细胞类型的表达水平上调，凸显了炎症在骨关节炎发病机制中的关键作用。在验证实验中，我们证实了膝骨关节炎（Knee Osteoarthritis, KOA）患者血清中β淀粉样蛋白水平升高，且其与APOE2及APOE4呈正相关。值得注意的是，载脂蛋白E3被确定为膝骨关节炎的独立保护因子。
结论：本项生物信息学分析筛选出了膝骨关节炎的DAMPs相关基因，并探索了其潜在功能与调控网络。我们通过实验证实了β淀粉样蛋白在膝骨关节炎中的高表达，并首次揭示了膝骨关节炎中β淀粉样蛋白与APOE2、APOE4的相关性，这为探索膝骨关节炎的发病机制及研究其治疗靶点提供了新的方向。