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.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.
