Naslov
Enhanced osteoclastogenesis in inflammatory arthritides is paralleled with the increased expression of proinflammatory mediators CCL2, IL-18 and FasL

Autori
Ikić, Marina ; Jajić, Zrinka ; Lazić, Elvira ; Kovačić, Nataša ; Marušić, Ana ; Grčević, Danka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Knjiga sažetaka / Stipić Marković, Asja - Zagreb : Hrvatsko društvo alergologa i kliničkih imunologa, 2012, 18-18

Skup
2012 Godišnji sastanak hrvatskih alergologa i kliničkih imunologa

Mjesto i datum
Zagreb, Hrvatska, 22.11.2012. - 24.11.2012

Vrsta sudjelovanja
Ostalo

Vrsta recenzije
Domaća recenzija

Ključne riječi
osteoclasts; rheumatoid arthritis; psoriatic arthritis; cytokines; bone loss

Sažetak
Inflammatory arthritides comprise a heterogeneous group of joint disorders that are characterized by chronic inflammatory response as well as intra-articular and generalized bone loss due to deregulation of bone homeostasis ; bone resorption by osteoclasts (OCs) and bone formation by osteoblasts. Many cytokines are involved in the pathogenesis of arthritis, acting as osteoclastogenic factors, but their effects are not fully revealed. Aim: The aim of our study was to assess the osteoclastogenic potential of peripheral-blood mononuclear cells (PBMC) and synovial-fluid derived mononuclear cells (SFMC), and its association with the disease type and activity. Further, we correlated the number of in vitro differentiated OCs with the parameters of systemic inflammation as well as circulating and intra-articular levels of proinflammatory/immunoregulatory mediators. Methods: PBMC were collected from control subjects (n=14), whereas PBMC and SFMC were collected from RA patients (n=10) and SpA patients (n=15), either with ankylosing spondylitis (AS=5) or psoriatic arthritis (PsA=10), after the informed consent. OCs were stimulated with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL), and detected as tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells. RNA was extracted from PBMC/SFMC cells, 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, TNF-α, and FasL). In addition, serum and synovial fluid levels of the same mediators were determined by ELISA. Results: Number of OCs differentiated from PBMC was significantly higher in patients with RA and PsA compared with controls and AS, with the most prominent osteoclastogenic potential in RA patients, paralleled by higher gene expression of RANK and TRAP. There was no difference in the number of OCs differentiated from SFMC of arthritic patients. However, gene expression of RANK and TRAP was higher in PsA compared with RA or AS. Inflammatory mediators were more elevated in SF compared with their serum values, with RA SF having the peak values especially for CCL2, TNF-α and IL-17. Positive correlations of the OC number with ESR, serum level of CCL2, and PBMC gene expression of IL-18 and FasL were observed. Conclusion: Osteoclastogenic potential is enhanced in patients with RA and PsA and is accompanied by disordered systemic and local expression of proinflammatory mediators and paralleled by increased inflammation. This may contribute to the development of new therapeutic interventions targeting simultaneously both destruction and inflammation.

Izvorni jezik
Engleski

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