FEATURES OF BONE REMODELING DURING THE USE OF ANTISENSE OLIGONUCLEOTIDES IN A RHEUMATOID ARTHRITIS MODEL

Introduction. Despite the vast number of drugs against rheumatoid arthritis, new methods and targets are still being searched for to treat this disease. In addition to changes in the joints, bone tissue also suffers significantly from rheumatoid arthritis. Aim. To research the histological features of bone tissue in the adjuvant-induced arthritis model, as well as the expression of matrix metalloproteinase 1 and 3 after the use of antisense oligonucleotides. Materials and Methods. Rheumatoid arthritis model was obtained by introducing the complete adjuvant Freind into the base of the tail of laboratory rats. For the therapy of the resulting disease, Tocilizumab and antisense oligonucleotides were used, which block the synthesis of the factor of tumor necrosis and interleukin 6, both separately and together. The morphological changes in the tails of rats and the activity of matrix metalloproteinase in various cell populations were investigated. To identify statistically significant differences between the groups, the Kruskal — Wallis test and Mann– Whitney U test were used. Results and Discussion. In the rheumatoid arthritis model, significant erosion of bone and cartilage tissue, abundant inflammatory infiltrate around the bone and in the bone marrow cavity, and slower bone growth were revealed. The use of antisense oligonucleotides significantly slowed down the progression of the disease. Levels of metalloproteinases in bone tissue were lower in some experimental groups compared to the untreated group. Conclusions. The use of antisense oligonucleotides slows down the inflammation development and prevents bone tissue resorption in damaged bones. The most effective were injections of oligonucleotide, which blocks interleukin-6. Combination of two oligonucleotides proved to be most effective in reducing the activity of matrix metalloproteinases that reorganize the extracellular matrix of bone in arthritis, as well as reducing the synthesis of tumor necrosis factor. Keywords: rheumatoid arthritis, antisense oligonucleotides, bone tissue.