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

Nikita Shabaldin , Andrey V. Shabaldin , Lev A. Bogdanov , Liudmila N. Igisheva , Sergei F. Zinchuk , Aleksandr E. Chervov

Pediatric Traumatology, Orthopaedics and Reconstructive Surgery ›› 2022, Vol. 10 ›› Issue (2) : 171 -182.

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Pediatric Traumatology, Orthopaedics and Reconstructive Surgery ›› 2022, Vol. 10 ›› Issue (2) : 171 -182. DOI: 10.17816/PTORS98467
Experimental and theoretical research
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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.

Keywords

Legg–Calve–Perthes disease / genetically engineered drugs / osteodestruction / monoclonal blockers of proinflammatory cytokines / cytokine status

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Nikita Shabaldin, Andrey V. Shabaldin, Lev A. Bogdanov, Liudmila N. Igisheva, Sergei F. Zinchuk, Aleksandr E. Chervov. The effect of proinflammatory cytokine inhibtors on the course of aseptic necrosis of the femoral head in a model experiment. Pediatric Traumatology, Orthopaedics and Reconstructive Surgery, 2022, 10(2): 171-182 DOI:10.17816/PTORS98467

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References

[1]

Kuzhelivskiy II. Bolezn’ Pertesa: sovremennoe sostoyanie problemy i puti ee resheniya. Sibirskiy meditsinskiy zhurnal (Irkutsk). 2015;135(2):117−121. (In Russ.)

[2]

Кужеливский И.И. Болезнь Пертеса: современное состояние проблемы и пути ее решения // Сибирский медицинский журнал (Иркутск). 2015. Т. 135. № 4. С. 117−121.

[3]

Barsukov DB, Krasnov AI, Baskov VE, et al. Korrigiruyushchaya osteotomiya bedra v kompleksnom lechenii detey s bolezn’yu Legga–Kal've–Pertesa. Geniy ortopedii. 2017;1:63−70. (In Russ.). DOI: 10.18019/1028-4427-2017-23-1-63-70

[4]

Барсуков Д.Б., Краснов А.И., Басков В.Е. и др. Корригирующая остеотомия бедра в комплексном лечении детей с болезнью Легга – Кальве – Пертеса // Гений ортопедии. 2017. № 1. С. 63−70. DOI: 10.18019/1028-4427-2017-23-1-63-70

[5]

Meiss AL, Barvencik F, Babin K, Eggers-Stroeder G. Denosumab and surgery for the treatment of Perthes’ disease in a 9-year-old boy: favorable course documented by comprehensive imaging – a case report. Acta Orthop. 2017;88(3):354−357. DOI: 10.1080/17453674.2017.1298020

[6]

Meiss A.L., Barvencik F., Babin K., Eggers-Stroeder G. Denosumab and surgery for the treatment of Perthes’ disease in a 9-year-old boy: favorable course documented by comprehensive imaging – a case report // Acta Orthop. 2017. Vol. 88. No. 3. P. 354−357. DOI: 10.1080/17453674.2017.1298020

[7]

Adapala NS, Kim HK. Comprehensive genome-wide transcriptomic analysis of immature articular cartilage following ischemic osteonecrosis of the femoral head in piglets. PloS One. 2016;11(4). DOI: 10.1371/journal.pone.0153174

[8]

Adapala N.S., Kim H.K. Comprehensive genome-wide transcriptomic analysis of immature articular cartilage following ischemic osteonecrosis of the femoral head in piglets // PloS One. 2016. Vol. 11. No. 4. DOI: 10.1371/journal.pone.0153174

[9]

Grebennikova TA, Belaya ZHE, Rozhinskaya LYa., Mel’nichenko GA. Kanonicheskiy signal’nyy put’ wnt/β-katenin: ot istorii otkrytiya do klinicheskogo primeneniya. Terapevticheskiy arkhiv. 2016;88(10):74−81. (In Russ.). DOI: 10.17116/terarkh201688674-81

[10]

Гребенникова T.А., Белая Ж.Е., Рожинская Л.Я., Мельниченко Г.А. Канонический сигнальный путь wnt/β-катенин: от истории открытия до клинического применения // Терапевтический архив. 2016. Т. 88. № 10. С. 74−81. DOI: 10.17116/terarkh201688674-81

[11]

Dmitrieva LA, Korshunova EYu, Lebedev VF. Rol’ interferonov v regulyatsii osteogennykh i osteorezorbtivnykh protsessov. Byulleten’ VSNC SO RAMN. 2012;87(5−2):136−140. (In Russ.)

[12]

Дмитриева Л.А., Коршунова Е.Ю., Лебедев В.Ф. Роль интерферонов в регуляции остеогенных и остеорезорбтивных процессов // Бюллетень ВСНЦ СО РАМН. 2012. T. 87. № 5−2. C. 136−140.

[13]

Gershteyn ES, Timofeev YuS, Zuev AA, Kushlinskiy NE. Ligand-retseptornaya sistema RANK/RANKL/OPG i ee rol’ pri pervichnykh novoobrazovaniyakh kostey (analiz literatury i sobstvennye rezul’taty). Uspekhi molekulyarnoy onkologii. 2015;3:51−59. (In Russ.)

[14]

Герштейн Е.С., Тимофеев Ю.С., Зуев А.А., Кушлинский Н.Е. Лиганд-рецепторная система и ее роль при первичных новообразованиях костей (анализ литературы и собственные результаты) // Успехи молекулярной онкологии. 2015. № 3. С. 51−59.

[15]

Kamiya N, Yamaguchi R, Adapala NS, et al. Legg-Calvé-Perthes disease produces chronic hip synovitis and elevation of interleukin-6 in the synovial fluid. J Bone Mineral Res. 2015;30(6):1009–1013. DOI: 10.1002/jbmr.2435

[16]

Kamiya N., Yamaguchi R., Adapala N.S. et al. Legg-Calvé-Perthes disease produces chronic hip synovitis and elevation of interleukin-6 in the synovial fluid // J. Bone Mineral Res. 2015. Vol. 30. No. 6. P. 1009–1013. DOI: 10.1002/jbmr.2435

[17]

Ren Y, Deng Z, Gokani V, et al. Anti-interleukin-6 therapy decreases hip synovitis and bone resorption and increases bone formation following ischemic osteonecrosis of the femoral head. J Bone Mineral Res. 2021. DOI: 10.1002/jbmr.4191

[18]

Ren Y., Deng Z., Gokani V. et al. Anti-interleukin-6 therapy decreases hip synovitis and bone resorption and increases bone formation following ischemic osteonecrosis of the femoral head // J. Bone Mineral Res. 2021. DOI: 10.1002/jbmr.4191

[19]

Kamiya N, Kuroyanagi G, Aruwajoye O, Kim HKW. IL6 receptor blockade preserves articular cartilage and increases bone volume following ischemic osteonecrosis in immature mice. Osteoarthritis and Cartilage. 2019;27(2):326−335 DOI: 10.1016/j.joca.2018.10.010

[20]

Kamiya N., Kuroyanagi G., Aruwajoye O., Kim H.K.W. IL6 receptor blockade preserves articular cartilage and increases bone volume following ischemic osteonecrosis in immature mice // Osteoarthritis and Cartilage. 2019. Vol. 27. No. 2. P. 326−335. DOI: 10.1016/j.joca.2018.10.010

[21]

Yamaguchi R, Kamiya N, Adapala NS, et al. HIF-1-dependent IL-6 activation in articular chondrocytes initiating synovitis in femoral head ischemic osteonecrosis. J Bone Joint Surg. 2016;98:1122−1131. DOI: 10.2106/JBJS.15.01209

[22]

Yamaguchi R., Kamiya N., Adapala N.S. et al. HIF-1-dependent IL-6 activation in articular chondrocytes initiating synovitis in femoral head ischemic osteonecrosis // J. Bone Joint Surg. 2016. Vol. 98. P. 1122−1131. DOI: 10.2106/JBJS.15.01209

[23]

Yuan HF, Guo CA, Yan ZQ. The use of bisphosphonate in the treatment of osteonecrosis of the femoral head: a meta-analysis of randomized control trials. Osteoporos Int. 2016;27:295–299. DOI: 10.1007/s00198-015-3317-5

[24]

Yuan H.F., Guo C.A., Yan Z.Q. The use of bisphosphonate in the treatment of osteonecrosis of the femoral head: a meta-analysis of randomized control trials // Osteoporos. Int. 2016. Vol. 27. P. 295–299. DOI: 10.1007/s00198-015-3317-5

[25]

Adapala NS, Kim HKW. Comprehensive genome-wide transcriptomic analysis of immature articular cartilage following ischemic osteonecrosis of the femoral head in piglets. Plos One. 2016;11(4):e0153174. DOI: 10.1371/journal.pone.0153174

[26]

Adapala N.S., Kim H.K.W. Comprehensive genome-wide transcriptomic analysis of immature articular cartilage following ischemic osteonecrosis of the femoral head in piglets // Plos One. 2016. Vol. 11. No. 4. P. e0153174. DOI: 10.1371/journal.pone.0153174

[27]

Kamiya N, Kim HKW. Elevation of proinflammatory cytokine HMGB1 in the synovial fluid of patients with Legg-Calvé-Perthes disease and correlation with IL-6. JBMR Plus. 2021;5(2):e10429. DOI: 10.1002/jbm4.10429

[28]

Kamiya N., Kim H.K.W. Elevation of proinflammatory cytokine HMGB1 in the synovial fluid of patients with Legg-Calvé-Perthes disease and correlation with IL-6 // JBMR Plus. 2021. Vol. 5. No. 2. P. e10429. DOI: 10.1002/jbm4.10429

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Shabaldin N., Shabaldin A.V., Bogdanov L.A., Igisheva L.N., Zinchuk S.F., Chervov A.E.

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