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Patients with osteoarthritis and rheumatoid arthritis but not ankylosing spondilitys have down-regulated BMP-4 and RUNX2 expression

Three major forms of chronic joint diseases are classified in clinical practice: osteoarthritis (OA), rheumatoid arthritis (RA) and spondyloarthritis (SpA) that includes several forms (ankylosing spondylitis (AS), psoriatic arthritis (PA), etc.). They differ in the pathophysiological mechanisms and the intensity of cartilage and bone destruction, with RA as a prototype of "destructive" arthritis, OA "steady-state" arthritis and SpA "remodeling" arthritis. The aim of our study was to test changes in the expression of selected bone morphogenetic proteins (BMPs), known for their osteoinductive action, in the peripheral blood mononuclear cells (PBMC) of patients with RA, OA and SpA, and analyze them in relation to the expression of Runx2, an essential transcriptional factor for osteoblast differentiation. Blood samples were collected from healthy controls (Ctrl ; n = 31, age range 24-61) and RA (n = 52, age range 27-57), OA (n = 15, age range 45-79) and SpA patients, either with AS (n = 26, age range 32-46) or PA (n = 20, age range 34-52), after the informed consent. RNA was extracted from PBMCs, converted to cDNA, amplified by quantitative PCR using TaqMan assays for BMP-2, -4 and Runx2, and expressed as the relative amounts of RNA (mean&#177; SD) for target genes normalized to GPDH. BMP-2 expression was not significantly different among groups, whereas BMP-4 expression was significantly down-regulated in RA and OA patients compared to SpA patients and control subjects (RA 2.35&#61617; 1.55 and OA 2.36&#61617; 1.80 vs. AS 5.86&#61617; 4.67, PA 4.17&#61617; 2.44 and Ctrl 5.94&#61617; 4.20, p<0.001, ANOVA). In addition, Runx2 was also significantly down-regulated in RA and OA patients compared to other groups (RA 3.01&#61617; 1.42 and OA 4.47&#61617; 4.55 vs. AS 8.95&#61617; 3.78, PA 6.17&#61617; 1.77 and Ctrl 7.89&#61617; 2.63, p<0.001, ANOVA). Our results indicate that RA and OA have decreased expression of BMP-4 and Runx2 in contrast to SpA, which reflects insufficient osteogenesis and joint reparation in those types of arthritis. Our further investigation will try to identify more bone-regulatory factors changed systemically in arthritic disease and their effects on bone cell survival, differentiation and activity, which may be helpful for novel therapeutic strategies aimed to restore joint homeostasis.

chronic joint diseases; BMP; Runx2

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