Succinate-Receptor System of Bone and Cartilage Tissue in Patients With Metabolic Phenotype of Osteoarthritis

Abstract

Introduction. Melatonin, by inducing the expression of antioxidant enzymes and signaling proteins, enhances the effects in the development of pathological processes occurring against the background of oxidative stress, therefore the stabilization of the protective principles of melatonin is a rel-evant area of research, allowing us to identify new ways of development and treatment of osteoarthritis. The aim. To study the effect of melatonin on the succinate receptor system of chondrocytes in osteoarthritis under conditions of oxidative stress in vitro. Materials and methods. The in vitro study was carried out on chondrocyte cell cultures. Melatonin was added to chondrocytes to obtain final con-centrations of 100 μM and 500 μM; and hydrogen peroxide (H2O2) – 200 µM. The duration of exposure was 24 hours for melatonin and 12 hours for H2O2. Succinate levels and expression of its receptor (SUCNR1) were determined in mitochondria and chondrocyte lysates. Results. It was found that the addition of H2O2 at a dose of 200 μM to the nutrient medium for 12 hours led to a fold increase in the level of succinate and SUCNR1 expression in chondrocyte cells. Pre-incubation of chondrocyte cells with melatonin at concentrations of 100 µM and 500 µM, followed by modeling of oxidative stress (H2O2 200 µM) led to a decrease in the expression of the succinate receptor system. Conclusion. When Н2О2 is added to the cellular environment of chondrocytes, high expression of SUCNR1 and an increase in succinate levels are ob-served. Melatonin treatment limits Н2О2-induced succinate accumulation and reduces SUCNR1 expression in human chondrocyte cells of the metabolic phenotype of osteoarthritis