Zhang Xin, Ma Sisi, Naz Syeda Iffat, Soderblom Erik J, Jain Vaibhav, Aliferis Constantin, Kraus Virginia Byers
Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC 27701, USA.
Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC 27701, USA.
Int J Mol Sci. 2024 Nov 21;25(23):12504. doi: 10.3390/ijms252312504.
Certain molecules found on the surface or within the cargo of extracellular vesicles (EVs) are linked to osteoarthritis (OA) severity and progression. We aimed to identify plasma pathogenic EV subpopulations that can predict knee radiographic OA (rOA) progression. We analyzed the mass spectrometry-based proteomic data of plasma EVs and synovial fluid (SF) EVs from knee OA patients (n = 16, 50% female). The identified surface markers of interest were further evaluated in plasma EVs from an independent cohort of knee OA patients (n = 30, 47% female) using flow cytometry. A total of 199 peptides with significant correlation between plasma and SF EVs were identified. Of these, 41.7% were linked to immune system processes, 15.5% to inflammatory responses, and 16.7% to the complement system. Crucially, five previously identified knee rOA severity-indicating surface markers-FGA, FGB, FGG, TLN1, and AMBP-were confirmed on plasma EV subpopulations in an independent cohort. These markers' baseline frequencies on large plasma EVs predicted rOA progression with an AUC of 0.655-0.711. Notably, TLN1 was expressed in OA joint tissue, whereas FGA, FGB, FGG, and AMBP were predominantly liver derived. These surface markers define specific pathogenic EV subpopulations, offering potential OA prognostic biomarkers and novel therapeutic targets for disease modification.
细胞外囊泡（EVs）表面或其内容物中发现的某些分子与骨关节炎（OA）的严重程度和进展有关。我们旨在确定能够预测膝关节影像学OA（rOA）进展的血浆致病性EV亚群。我们分析了膝关节OA患者（n = 16，50%为女性）血浆EVs和滑液（SF）EVs的基于质谱的蛋白质组学数据。使用流式细胞术在另一组独立的膝关节OA患者（n = 30，47%为女性）的血浆EVs中进一步评估了所鉴定的感兴趣的表面标志物。共鉴定出199种在血浆和SF EVs之间具有显著相关性的肽段。其中，41.7%与免疫系统过程相关，15.5%与炎症反应相关，16.7%与补体系统相关。至关重要的是，在一个独立队列的血浆EV亚群中证实了五个先前鉴定的膝关节rOA严重程度指示表面标志物——纤维蛋白原α链（FGA）、纤维蛋白原β链（FGB）、纤维蛋白原γ链（FGG）、弹力蛋白（TLN1）和α1-微球蛋白/bikunin前体（AMBP）。这些标志物在大型血浆EVs上的基线频率预测rOA进展的曲线下面积（AUC）为0.655 - 0.711。值得注意的是，TLN1在OA关节组织中表达，而FGA、FGB、FGG和AMBP主要来源于肝脏。这些表面标志物定义了特定的致病性EV亚群，为OA提供了潜在的预后生物标志物和疾病修饰的新型治疗靶点。
