Succinate-receptor system of bone and cartilage tissue in patients with metabolic phenotype of osteoarthritis

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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 relevant 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 concentrations 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 H₂O₂ is added to the cellular environment of chondrocytes, high expression of SUCNR1 and an increase in succinate levels are observed. Melatonin treatment limits H₂O₂-induced succinate accumulation and reduces SUCNR1 expression in human chondrocyte cells of the metabolic phenotype of osteoarthritis.

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About the authors

D. R. Shodiev

Ryazan State Medical University named after academician I. P. Pavlov

Author for correspondence.
Email: shodiev.dima@yandex.ru
ORCID iD: 0000-0002-4530-2964

Post-graduate Student

Russian Federation, Vysokovoltnaya str., 9, 390026, Ryazan

V. I. Zvyagina

Ryazan State Medical University named after academician I. P. Pavlov

Email: vizvyagina@yandex.ru
ORCID iD: 0000-0003-2800-5789

Dr. Sc. (Med.), Associated Professor of Department of Biochemistry

Russian Federation, Vysokovoltnaya str., 9, 390026, Ryazan

M. N. Ryabova

Ryazan State Medical University named after academician I. P. Pavlov

Email: rmn62doc@yandex.ru
ORCID iD: 0000-0002-1707-2567

Ph. D. (Med.), Associated Professor of Department of General Surgery, Traumatology and Orthopedics

Russian Federation, Vysokovoltnaya str., 9, 390026, Ryazan

Yu. A. Marsyanova

Ryazan State Medical University named after academician I. P. Pavlov

Email: yuliyamarsyanova@yahoo.com
ORCID iD: 0000-0003-4948-4504

Associated Professor of Department of Biochemistry

Russian Federation, Vysokovoltnaya str., 9, 390026, Ryazan

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2. Fig. 1. Amount of SUCNR1 and succinate in chondrocyte cells after exposure to 100 and 500 μM melatonin for 24 hours; ns – p ≥ 0,05

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3. Fig. 2. Amount of SUCNR1 and succinate in chondrocyte cells after exposure to H₂O₂ 200 μM for 12 hours; ** – p <0,01

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4. Fig. 3. Amount of SUCNR1 and succinate in chondrocyte cells after exposure of cells pre-treated with melatonin to H₂O₂ 200 μM for 12 hours; ns – p ≥0,05; * – p <0,05; ** – p <0,01

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5. Fig. 4. Amount of SUCNR1 and succinate in chondrocyte cells after exposure to H₂O₂ 200 μM for 12 hours on cells pre-treated with melatonin in comparison with the initial values; ns – p ≥0,05; ** – p <0,01

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