Changes in Polarity and Regeneration-Related Gene Expression in In Vitro Bone Marrow Mesenchymal Stem Cells in a Rheumatoid Arthritis Injury Model and Pharmacological Modulation

Abstract

Purpose: The aim of this study was to investigate the changes in polarity and regeneration at the gene-protein level with pharmacological modulation of rheumatoid arthritis (RA) disease, which occurs as a result of chronic, inflammation-induced tissue erosion whose pathogenesis steps are well understood. Materials and Methods: To investigate the damage caused by the pathogenetic steps of the disease to intracellular polarity and regeneration, bone marrow mesenchymal stem cells subjected to injury mimicry using IL-1β and IL-6 were treated with a combination of the IL-1β antagonist antibody canakinumab and the IL-6 antagonist antibody tocilizumab. The effects on cell viability, cytotoxicity, and the expression of genes related to intracellular polarity and regeneration were examined. Results: As a result of the analyses, as expected, IL-1β and IL-6 caused a reduction in viability and an acceleration in cytotoxicity in human bone marrow stem cells imitating RA damage. In addition, in gene expression analyses, low significant changes were observed in the expression of genes consisted in polarity pathways, but significant changes were found in the expression of genes take place in regeneration mechanisms. In addition, the application of antagonist agents reversed this situation and limited normalization and even changes that increased the viability of the cells in viability tests were observed. Conclusion: In this case, in the RA-like pathogenesis model obtained after injury mimicry, it is thought that the inflammation occurring during the disease's developmental stages causes stem cells to lose their properties such as adhesion and navigation, thereby affecting the efficiency of the regenerative properties they maintain.

Keywords

• arthritis
• bone marrow mesenchymal stem cell
• ınterleukin
• monoclonal antibody