The level of matrix metalloproteinases in the blood in a model of adjuvant-induced arthritis and its correction with antisense oligonucleotides

Makalish T.P., Pilyavsky N.N., Golovkin I.O., Maslova G.V.

Vernadsky Crimean Federal University, Simferopol, Russia

Rheumatoid arthritis is characterized by significant rearrangements in bone and cartilage tissues mediated by matrix metalloproteinases (MMPs). One of the directions in the development of new drugs for rheumatoid arthritis is the search for new targets, including MMPs or their inhibitors. The work aimed to determine the levels of MMP-1, 3, and 9 in the peripheral blood of laboratory rats with a model of adjuvant-induced arthritis during the correction of this condition with antisense oligonucleotides that block the synthesis of tumor necrosis factor and interleukin 6. In laboratory Wistar rats, arthritis was modeled by administering Freund's adjuvant and then correcting the disease by introducing antisense oligonucleotides subcutaneously and using electrophoresis. The level of MMP in peripheral blood was determined at the beginning of treatment, after 1, 2, and 3 months. Chronic inflammation in the experiment was accompanied by an increase in the level of MMP-1, 3, and 9 in the peripheral blood by 2, 4.5, and 0.5 times, respectively. Blocking the proinflammatory cytokines TNF-α and IL-6 with antisense oligonucleotides was effective in reducing MMP levels. In most cases, it decreased significantly faster than in the untreated arthritis model. These changes were most pronounced in groups using tocilizumab, as well as in group with an electrophoretic form of administration of a combination of two oligonucleotides.