The effect of proinflammatory cytokine inhibtors on the course of aseptic necrosis of the femoral head in a model experiment

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Abstract

BACKGROUND: One of the most relevant areas of study of Perthes’ disease is the search and scientific justification of new targets for the treatment of osteodestructive processes. At the same time, an important link in the regulation of bone homeostasis is the cytokine system that affects the processes of differentiation and activation of osteoclasts through the RANK-RANKL-OPG signaling pathway. Inhibition of the biological action of proinflammatory cytokines in the early stages of aseptic necrosis is a promising direction in the study of antiresorptive therapy.

АIM: To assess the effectiveness of monoclonal blockers of proinflammatory cytokines in the treatment of aseptic necrosis of the femoral head in a model experiment on Wistar rats.

MATERIALS AND METHODS: A model experiment was performed on small animals (24 Wistar rats). All animals underwent surgical induction of aseptic necrosis of the femoral head. The rats were divided into four groups: group 1 did not receive treatment, group 2 were administered a monoclonal IL-6 blocker, group 3 was administered a TNFα binding inhibitor, and group 4, a monoclonal IL-1β blocker. Moreover, histological, X-ray, biochemical, and immunological studies were equally performed.

RESULTS: We revealed the influence of monoclonal blockers of the biological action of proinflammatory cytokines on the processes of osteogenesis during the manifestation of aseptic necrosis of the femoral head. The most favorable outcomes of the course of aseptic necrosis of the femoral head in the form of greater preservation of the cartilaginous, bony structure were obtained in rats treated with a monoclonal blocker of the proinflammatory cytokine, IL-6.

CONCLUSIONS: Genetically engineered biological agents of receptor blockers of proinflammatory cytokines affect aseptic inflammation, especially during osteodestruction. Further studies of the properties of the IL-6 monoclonal blocker is a promising aspect in the study of its effect on bone metabolism disorders in osteolysis.

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About the authors

Nikita Shabaldin

Kemerovo State Medical University

Email: Shabaldin.nk@yandex.ru
ORCID iD: 0000-0001-8628-5649
SPIN-code: 6283-2581
Scopus Author ID: 57209570350

MD, PhD, Cand. Sci. (Med.)

Russian Federation, 22a Voroshilov str., Kemerovo, 650029

Andrey V. Shabaldin

Kemerovo State Medical University

Email: weit2007@yandex.ru
ORCID iD: 0000-0002-8785-7896
SPIN-code: 5281-0065

MD, PhD, Dr. Sci. (Med.), Assistant Professor

Russian Federation, 22a Voroshilov str., Kemerovo, 650029

Lev A. Bogdanov

Institute for Complex Issues of Cardiovascular Diseases

Email: bogdanovleone@gmail.com
ORCID iD: 0000-0003-4124-2316
SPIN-code: 9547-9196
ResearcherId: R-9744-2018

MD, Junior Research Associate

Russian Federation, 22a Voroshilov str., Kemerovo, 650029

Liudmila N. Igisheva

Kemerovo State Medical University; Institute for Complex Issues of Cardiovascular Diseases

Email: igisheval@yandex.ru
ORCID iD: 0000-0002-7102-3571
SPIN-code: 3025-1607

MD, PhD, Dr. Sci. (Med.)

Russian Federation, 22a Voroshilov str., Kemerovo, 650029; Kemerovo

Sergei F. Zinchuk

Kemerovo State Medical University

Email: zinchuk.sf@kemsma.ru
ORCID iD: 0000-0001-7774-4196
SPIN-code: 3199-8459

MD, PhD, Cand. Sci. (Med.), Assistant Professor

Russian Federation, 22a Voroshilov str., Kemerovo, 650029

Aleksandr E. Chervov

Kuzbass Clinical Pathology Bureau

Author for correspondence.
Email: acheront999@gmail.com
ORCID iD: 0000-0001-6168-4483

MD, pathologist

Russian Federation, 22a Voroshilov str., Kemerovo, 650029

References

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Supplementary files

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2. Fig. 1. Study of the step amplitude: a — group 1 (no treatment); b — group 3 (TNFα inhibitor); c — group 4 (IL-1β monoclonal receptor blocker); d — group 2 (IL-6 monoclonal receptor blocker)

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3. Fig. 2. Studies of a conditionally healthy limb: a — macroscopic specimen; b — X-ray examination; c — histological specimen stained with hematoxylin and eosin, 50× (normal bone architectonics were preserved); d — histological specimen stained with hematoxylin and eosin, 100×

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4. Fig. 3. Studies of a specimen showing aseptic necrosis of the femoral head (without treatment): a — macroscopic specimen; b — X-ray examination; c — histological specimen stained with hematoxylin and eosin, 50× (thinning of bone trabeculae, loss of a significant part of osteocytes, degenerative changes in the growth plate, and thinning of the articular cartilage with proliferation of fibrous tissue); d — histological specimen stained with hematoxylin and eosin, 200× (arrows indicate active osteoclasts)

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5. Fig. 4. Studies of a specimen of aseptic necrosis of the femoral head treated with an IL-6 monoclonal blocker IL-6: a — gross specimen; b — X-ray examination; c — histological specimen, stained with hematoxylin and eosin, 50× (slight decrease in the density of bone trabeculae but intact structure; dystrophic changes in the growth plate; thinning of the articular cartilage); d — histological specimen, stained with hematoxylin and eosin, 200× (arrows indicate active osteoblasts)

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6. Fig. 5. Studies of a specimen of aseptic necrosis of the femoral head treated with a TNFα monoclonal blocker: a — gross specimen; b — X-ray examination; c — histological specimen stained with hematoxylin and eosin, 50× (decreased bone trabeculae density, thinning of the articular cartilage, and randomly arranged chondrocytes); d — histological specimen stained with hematoxylin and eosin, 200× (arrows indicate foci of bone replace with connective tissue)

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7. Fig. 6. Studies of a specimen of aseptic necrosis of the femoral head treated with an IL-1β monoclonal blocker: a — gross specimen; b — X-ray examination; c — histological specimen, stained with hematoxylin and eosin, 50× (nonuniform decrease in the height of the articular cartilage, interruption of the growth zone by areas of connective tissue, and decreased bone trabeculae density); d — histological specimen stained with hematoxylin and eosin, 200× (arrow indicates the zone of dystrophic changes in the growth plate)

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Copyright (c) 2022 Shabaldin N., Shabaldin A.V., Bogdanov L.A., Igisheva L.N., Zinchuk S.F., Chervov A.E.

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