engleski

BMP-4 is down-regulated together with Runx2 and FasL in the peripheral blood of patients with rheumatoid arthritis and osteoarthritis

Background. Three major forms of chronic joint diseases are classified in clinical practice: osteoarthritis (OA), rheumatoid arthritis (RA) and spondyloarthritis (SpA) that includes ankylosing spondylitis (AS), psoriatic arthritis (PA), reactive arthritis, 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 severity of arthritis is determined by the balance between destructive and reparative pathways, mediated by a number of cytokines, growth factors, apoptotic molecules, etc. Objectives. The aim of our study was to test changes in the expression of selected bone morphogenetic proteins (BMPs), known for their osteoinductive anabolic action, in the peripheral blood mononuclear cells (PBMC) of patients with RA, OA and SpA. Expression of BMPs was further analyzed in relation to the expression of Runx2, an essential transcriptional factor for osteoblast differentiation and FasL, one of the catabolic regulators of bone metabolism. Methods. Blood samples were collected from healthy controls (Ctrl ; n = 31, age range 24-61) and RA patients (n = 52, age range 27-57), OA patients (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, BMP-4, FasL and Runx2, and expressed as the relative amounts of RNA (median (range)) for target genes normalized to GPDH. Results. BMP-2 expression was not significantly different among patients and controls, whereas BMP-4 expression was down-regulated in RA and OA patients compared with control subjects (RA 0.18 (0.01-0.65) and OA 0.18 (0.05-0.65) vs. Ctrl 0.52 (0.06-1.75), p<0.001, Kruskal-Wallis). Runx2 was also down- regulated in RA and OA patients compared with control (RA 2.66 (0.94-6.46) and OA 3.35 (1.51- 21.30) vs. Ctrl 7.77 (4.01-13.64), p<0.001, Kruskal-Wallis). Interestingly, FasL was down- regulated in RA, OA as well as in PA patients (RA 1.41 (0.33-7.51), OA 1.86 (0.29-7.59), PA 0.38 (0.05-0.94) vs. Ctrl 4.20 (1.62-10.48), p<0.001, Kruskal-Wallis). Expression of FasL in PA patients was also significantly different compared with AS patients (PA 0.38 (0.05-0.94) vs. AS 2.95 (1.05- 6.61), p<0.001, Mann-Whitney). Conclusions. Our results indicate that RA and OA patients have decreased expression of BMP-4 and Runx2, which reflects insufficient osteogenesis and joint reparation in those types of arthritis. FasL was also down-regulated in RA, OA and PA patients, which may indicate possible compensatory mechanism to reduce catabolic processes. 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.

BMPs; Runx2; FasL; arthritis

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