engleski

RANKL/RANK/OPG axis is deregulated in the peripheral blood mononuclear cells of patients with multiple sclerosis at clinical onset

Background/aim. Multiple sclerosis (MS) and its clinical forms are the most common autoimmune demyelinating diseases of the central nervous system. It has been proven that the MS patients have increased risk of osteoporosis with the disease progression. However, little is known about the bone metabolism at the time of clinical onset. Balance between the interaction of RANKL (receptor-activator of NF-B ligand) with activating receptor RANK on osteoclast progenitors and with decoy receptor OPG (osteoprotegerin) determines osteoclast differentiation and bone- resorptive potential. Our study aimed to asses changes in the RANKL/RANK/OPG axis in the diagnostic peripheral blood mononuclear cell (PBMC) samples of MS patients. Methods. Blood was collected from healthy controls (Ctrl ; n=11, age range 22-45) and MS patients (n=13, age range 22- 47) after the informed consent. MS patients had expanded disability status scale (EDSS) score no more than 4.0. RNA was extracted from PBMC, converted to cDNA, amplified by quantitative PCR using TaqMan assays, and expressed as the relative amounts of RNA (mean ± SD) for target genes normalized to GAPDH (house-keeping). Results. OPG expression was significantly decreased in MS patients (MS 0.12±0.06 vs. Ctrl 0.26±0.15, p=0.01), whereas RANK expression was significantly increased in MS patients compared to controls (MS 0.26±0.11 vs. Ctrl 0.17±0.08, p=0.04). RANKL expression was very low and similar in both groups. Conslusions. We found that RANKL/RANK/OPG axis is deregulated in MS patients at the time of clinical onset, promoting bone resorption. This indicates that the autoimmune process per se possibly induces osteoresorptive processes as a result of increased osteoclastogenesis.

multiple sclerosis ; cytokines ; osteoporosis

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