Table_2_Proteomic Changes of Osteoclast Differentiation in Rheumatoid and Psoriatic Arthritis Reveal Functional Differences.csv

BackgroundOsteoclasts play a crucial role in the maintenance, repair, and remodeling of bones of the adult vertebral skeleton due to their bone resorption capability. Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are associated with increased activity of osteoclasts.ObjectivesOur study aimed to investigate the dynamic proteomic changes during osteoclast differentiation in healthy donors, in RA, and PsA.MethodsBlood samples of healthy donors, RA, and PsA patients were collected, and monocytes were isolated and differentiated into osteoclasts in vitro using macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANK-L). Mass spectrometry-based proteomics was used to analyze proteins from cell lysates. The expression changes were analyzed with Gene Set Enrichment Analysis (GSEA).ResultsThe analysis of the proteomic changes revealed that during the differentiation of the human osteoclasts, expression of the proteins involved in metabolic activity, secretory function, and cell polarity is increased; by contrast, signaling pathways involved in the immune functions are downregulated. Interestingly, the differences between cells of healthy donors and RA/PsA patients are most pronounced after the final steps of differentiation to osteoclasts. In addition, both in RA and PsA the differentiation is characterized by decreased metabolic activity, associated with various immune pathway activities; furthermore by accelerated cytokine production in RA.ConclusionsOur results shed light on the characteristic proteomic changes during human osteoclast differentiation and expression differences in RA and PsA, which reveal important pathophysiological insights in both diseases.

背景：破骨细胞在维持、修复和重塑成年脊椎骨骼骨组织中扮演着至关重要的角色，这得益于其骨吸收能力。类风湿性关节炎（RA）和银屑病关节炎（PsA）与破骨细胞的活性增加有关。目标：本研究旨在探讨健康捐赠者、RA 和 PsA 患者中破骨细胞分化过程中的动态蛋白质组变化。方法：收集了健康捐赠者、RA 和 PsA 患者的血液样本，并通过体外使用巨噬细胞集落刺激因子（M-CSF）和核因子κB配体（RANK-L）受体激活因子将单核细胞分离并分化为破骨细胞。基于质谱的蛋白质组学被用于分析细胞裂解物中的蛋白质。利用基因集富集分析（GSEA）分析了表达变化。结果：蛋白质组变化的分析揭示了在人类破骨细胞分化过程中，参与代谢活性、分泌功能和细胞极性的蛋白质表达增加；相反，参与免疫功能的信号通路被下调。有趣的是，健康捐赠者和 RA/PsA 患者细胞之间的差异在分化为破骨细胞的最终步骤后最为明显。此外，在 RA 和 PsA 中，分化特征表现为代谢活性下降，与多种免疫通路活动相关；此外，在 RA 中，细胞因子产生加速。结论：我们的研究结果揭示了人类破骨细胞分化过程中的特征性蛋白质组变化以及 RA 和 PsA 中的表达差异，这些发现为两种疾病的病理生理学提供了重要的见解。