Proteomic changes of osteoclast differentiation in rheumatoid and psoriatic arthritis reveal functional differences

ABSTRACT: 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.

INSTRUMENT(S): maXis II

ORGANISM(S): Human

SUBMITTER: Laszlo Drahos  

PROVIDER: MSV000089073 | MassIVE | Wed Mar 16 11:47:00 GMT 2022

REPOSITORIES: MassIVE