Project description:Genome wide DNA methylation profiling of monocytes from healthy donors and rheumatoid arthritis patients. The Illumina Infinium MethylationEPIC Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs in CD11b+CD33+CD15neg monocytes isolated from PBMCs of 17 healthy donors and 47 rheumatoid arthritis patients with different disease activity scores (DAS28).
Project description:miRNA differential expression in Rheumatoid arthritis(RA) blood: Microarray analysis of miRNAs in blood from RA and healthy donors.
Project description:Background: Osteoclasts 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.
Objectives: Our study aimed to investigate the dynamic proteomic changes during osteoclast differentiation in healthy donors, in RA, and in PsA.
Methods: Healthy donors', RA, and PsA patients' blood samples were collected, monocytes were isolated and differentiated into osteoclasts in vitro using M-CSF and RANK-L treatment. Mass Spectrometry based proteomics were used to analyze proteins from cell lysates. The expression changes were analysed with Gene Set Enrichment Analysis (GSEA).
Results: The 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.
Conclusions: Our results shed light to the characteristic proteomic changes during human osteoclast differentiation and expression differences in RA and PsA, which reveal important pathophysiological insights in both diseases.