Effect of DNA methylation modulators on the production of osteoprotegerin by rheumatoid fibroblast-like synoviocytes in vitro: their migration and invasion

Abstract

Objective. The purpose of the research was to study the effect of DNA methylation modulators on the production of proinflammatory cytokines by fibroblast-like synovial cells (FLC).Materials and methods. We used the cells derived from the synovial tissue of 6 patients with active rheumatoid arthritis (RA) after 3–7 in vitro culturing passages.Results. There was an IL-1β-induced up-regulation of osteoprotegerin (OPG) synthesis in the RA FLC cultures. The addition of methylating compounds S-Adenosyl methionine (SAMe) and genistein into the cultures resulted in a statistically significant decrease in the production of OPG, while the addition of the demethylating agent hydralazine did not change the synthesis of the cytokine. All three DNA methylation modulators used at different concentrations significantly reduced the percentage of spontaneous migration and invasion of FLC in the Boyden chamber.Conclusion. Enzymes and molecular complexes involved in DNA methylation could be potential therapeutic targets, and in vitro FLC cultures of RA patients can be used as a model for preclinical screening of new drug compounds.