Epoetin-alfa-induced osteogenesis in the bone organoid model

Authors

DOI:

https://doi.org/10.18413/rrpharmacology.10.517

Abstract

Introduction: Erythropoietin interacts ETwith EPOR/βcR(CD131) and activates the non-canonical pathway JAK/STAT and PI3K/AKT. Phosphorylated STAT subunits were found to get dimerized and translocated into the nucleus to activate the expression of the Runx-2 and TGF-β genes. The purpose of the study was to evaluate the effectiveness of osteogenesis when using epoetin alpha as an osteoinducer in an experimental model of a bone organoid.

Materials and Methods: The study was conducted on human mesenchymal stem cells (hMSC) and trabecular bone organoids (TBO). Photometry and microscopy were used to assess the effects of drugs on proliferation and differentiation of hMSС and the formation of osteogenic tissue in TBO. The volume of connective tissue structures and the activity of mitochondria was determined in cells that form fibrovascular osteogenic tissue in TBO.

Results: Epoetin alpha was found to have a dose-dependent osteoinductive effect in TBO. At a dose of 200 IU/mL, epoetin alpha has an inhibitory effect, whereas at a dose of 20 IU/mL, it activates the proliferation and differentiation of hMSC in the osteogenic direction by inducing osteogenesis in TBO.

Conclusion: Epoetin alpha has a protective effect on osteogenesis in TBO inducing the proliferation of osteoblasts and endotheliocytes, stimulating the growth of connective tissue structures of the bone organoid with the formation of osteogenic tissue along with increasing the activity of mitochondria and reducing intracellular generation of reactive oxygen species.

Graphical Abstract

Keywords:

epoetin alfa, trabecular bone organoid, osteogenesis

References

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Author Contribution

Natalia A. Nadezhdina, Belgorod State National Research University

Otorhinolaryngologist, Children’s Regional Clinical Hospital, postgraduate student of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: nadezhdina.nat@yandex.ru; ORCID ID: https://orcid.org/0000-0002-6425-3635. The author took part in the design of the study, in conducting experimental work and analyzing the material.

Oleg S. Gudyrev, Belgorod State National Research University

Candidate of Sciences (Medicine), Associate Professor of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: gudyrev@mail.ru; ORCID ID:https://orcid.org/0000-0003-0097-000X. The author participated in the review and analysis of literary sources.

Sergey V. Nadezhdin, Belgorod State National Research University

Candidate of Sciences (Biology), Associate Professor, Department of Pharmacology and Clinical  Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: nadezhdin@bsu.edu.ru; ORCID ID: https://orcid.org/0000-0001-8444-6330. The author took part in the experimental work.

Lyudmila M. Danilenko, Belgorod State National Research University

Doctor Habil. of Sciences (Pharmacy), Professor of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: Danilenko_L@mail.ru; ORCID ID:https://orcid.org/0000-0001-6101-8712. The author analyzed the results and edited the text of the article.

Aleksandr A. Dolzhikov, Belgorod State National Research University

Doct.or Habil. of Sciences (Medicine), Professor of the Department of Human Anatomy and Histology, Belgorod State National Research University, Belgorod, Russia; e-mail: dolzhikov@bsu.edu.ru; ORCID ID: https://orcid.org/0000-0001-7425-8416. The author analyzed the results and edited the text of the article.

Tatyana G. Pokrovskaya, Belgorod State National Research University, Belgorod

Doctor Habil. of Sciences (Medicine), Professor of the  Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: pokrovskaia-tg@mail.ru; ORCID ID:https://orcid.org/0000-0001-6802-5368. The author analyzed the results and edited the text of the article.

Kristina K. Kremleva

Postgraduate student of Department of the Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: kremlevakristi@yandex.ru; ORCID ID: https://orcid.org/0009-0009-7595-6022. The author edited the text of the article.

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Published

28-12-2024

How to Cite

Nadezhdina NA, Gudyrev OS, Nadezhdin SV, Danilenko LM, Dolzhikov AA, Pokrovskaya TG, Kremleva KK (2024) Epoetin-alfa-induced osteogenesis in the bone organoid model. Research Results in Pharmacology 10(4): 29–41. https://doi.org/10.18413/rrpharmacology.10.517

Issue

Vol. 10 No. 4 (2024)

Section

Experimental Pharmacology

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Copyright (c) 2024 Nadezhdina NA, Gudyrev OS, Nadezhdin SV, Danilenko LM, Dolzhikov AA, Kremleva KK, Pokrovskaya TG

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