engleski

Greater osteoclastogenic potential in patients with rheumatoid arthritis for peripheral blood but similar for synovial fluid mononuclear cells compared to patients with spondyloarthritis

Chronic joint diseases affect more than a third of the world's population and represent a major health problem because they cause disability, have progressive morbidity, and the therapy is only partially successful. Several forms are classified in clinical practice: osteoarthritis (OA), rheumatoid arthritis (RA), and spondyloarthritis (SpA). Many cytokines and growth factors play a role in the pathogenesis of different forms of arthritis, and can act as osteoclastogenic factors. Their expression is altered not only at local sites of joint lesions but also systemically, but the relative contribution of systemic versus local changes in osteoclast differentiation and activity has not been fully revealed. The aim of our study was to assess the osteoclastogenic potential from peripheral-blood mononuclear cells (PBMC) and local synovial-fluid derived mononuclear cells (SFMC) in patients with RA and SpA. In our study, PBMC and SFMC were collected from RA patients (n=10) and SpA patients (n=14), either with AS or PsA, after the informed consent. Osteoclast differentiation was stimulated with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL). Osteoclasts (OCs) were detected as tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells (three or more nuclei per cell). RNA was extracted from PBMC/SFMC and osteoclastogenic cultures, reversely transcribed to cDNA, and amplified by quantitative PCR for the expression of osteoclast differentiation genes (RANK, cFms, TRAP) and inflammatory mediators (CCL2, VEGF, IL-17, IL-18, TNFα). In addition, serum and synovial fluid levels of the same mediators were determined by ELISA. In vitro osteoclastogenesis showed higher osteoclastogenic potential of PBMC but similar potential of SFMC for RA patients compared to AS and PsA patients. In parallel, gene expression of osteoclast differentiation genes RANK and TRAP was higher in osteoclastogenic cultures derived from PBMC of RA patients. Gene expression of inflammatory mediators CCL2, VEGF and IL18 were higher in PBMC and SFMC of RA patients compared with other groups. Levels of inflammatory mediators CCL2 and VEGF measured in the synovial fluid by ELISA were in concordance with the gene expression level. Our results indicate that osteoclast progenitors are contained among both PBMCs and SFMCs but not with the same frequency in different forms of arthritis and even within the PBMC and SFMC of the same patient. Patients with RA have higher number of osteoclast precursors contained among PBMCs compared with SpA patients. Moreover, greater osteoclastogenic potential in RA was paralleled with the increased expression of pro-inflammatory mediators (CCL2, VEGF) in serum and synovial fluid. These findings may be relevant for the development of therapeutic approaches aimed to modulate their action.

Cartilage; synovium and osteoimmunology

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