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

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Abstract

Introduction. Currently, osteoarthritis (OA) has been identified as a polyetiological disease, where several phenotypes have been identified based on the leading frequency. Obviously, each clinical phenotype corresponds only to its fundamental changes on the part of various organs and systems. Until recently, special attention was paid to the study of metabolic processes in osteoarthritis (OA) and was paid to the state of the cartilage, but more and more interest was focused on the biochemistry of the subchondral bone, its microarchitectonics and signal function.

Aid. To study the features of the manifestation of the succinate-receptor system of bone and cartilage tissue in patients with the metabolic phenotype of osteoarthritis.

Material and methods. 42 patients took part in the study and were divided into 2 groups: 1 group – patients without articular disease, normal body mass index; 2 group – patients with metabolic phenotype of OA. The subjects were collected complaints, anamnesis, as well as general clinical and orthopedic examination. The levels of succinate, succinate receptor (SUCNR1) and succinate dehydrogenase (SDH) are measured in bone and cartilage tissue homogenates.

Results. In the 2 group, an increase in SUCNR1 expression was detected in all studied areas of the joint in comparison with the 1 group. In the 2 group, the differences were tissue-specific in the distribution of SUCNR1 with a predominant increase in the amount of the receptor in the subchondral bone compared to the loaded (p=0.031) and non-loaded zone of cartilage (p=0.001). In the 1 group, the studied areas of cartilage and bone did not differ in the amount of SUCNR1 from each other. In the group of patients with the metabolic phenotype of OA, an increase in mitochondrial succinate was found both in the subchondral bone tissue and in different zones of cartilage compared to the 1 group. The final indicators of SDH activity in the mitochondria of the studied joint zones that we obtained turned out to be low in both groups, however, relatively high enzyme activity was observed in the subchondral zone of the bone of the group of metabolic phenotype of OA.

Conclusion. In patients with the metabolic phenotype of OA, high expression of SUCNR1 in joint tissues is observed, which is tissue-specific with a predominant increase in the amount of SUCNR1 in the subchondral bone. We found higher levels of succinate in the subchondral bone and cartilaginous areas of joints in patients with the metabolic phenotype of OA and suggest that the succinate-SUCNR1 interaction in affected joints in OA is adaptive in nature.

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About the authors

D. R. Shodiev

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

Author for correspondence.
Email: shodiev.dima@yandex.ru
ORCID iD: 0000-0002-4530-2964
SPIN-code: 3556-4398

Post-graduate Student

Russian Federation, Ryazan

V. I. Zvyagina

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

Email: vizvyagina@yandex.ru
ORCID iD: 0000-0003-2800-5789
SPIN-code: 7553-8641
Scopus Author ID: 57189726173

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

Russian Federation, Ryazan

M. N. Ryabova

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

Email: rmn62doc@yandex.ru
ORCID iD: 0000-0002-1707-2567
SPIN-code: 2077-3173

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

Russian Federation, Ryazan

Y. A. Marsyanova

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

Email: yuliyamarsyanova@yahoo.com
ORCID iD: 0000-0003-4948-4504
SPIN-code: 4075-3169

Assistant, Department of Biochemistry

Russian Federation, Ryazan

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2. Fig. 1. Amount of succinate receptor (SUCNR1) in homogenates of joint tissues in patients of groups 1 and 2, ng/mL: k, subchondral bone; hn, cartilage of loaded zone; hnn, cartilage of unloaded zone (* - pk1-2<0.01; ** - phn1-2<0.01; *** - phn1-2<0.01)

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3. Fig. 2. Amount of succinate receptor SUCNR1 in the homogenates of joint tissues in group 2 patients, ng/mL: k - subchondral bone; hn - cartilage of the loaded zone; hn - cartilage of the unloaded zone (* - rxn-c<0.01; ** - rxn-c<0.01)

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4. Fig. 3. Succinate content in mitochondria of joint tissue homogenates from patients of groups 1 and 2, μmol/mL: k - subchondral bone; hn - cartilage of the loaded zone; hnn - cartilage of the unloaded zone (* - pk1-2<0.01; ** - phn1-2<0.01; *** - phn1-2<0.01).

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5. Fig 4. Correlation analysis of subchondral bone SUCNR1 level and body fat percentage in patients with metabolic phenotype of OA

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