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The Non-Erythropoietic EPO Analogue Cibinetide Inhibits Osteoclastogenesis In Vitro and Increases Bone Mineral Density in Mice

Authors :
Zamzam Awida
Almog Bachar
Hussam Saed
Anton Gorodov
Nathalie Ben-Califa
Maria Ibrahim
Albert Kolomansky
Jennifer Ana Iden
Liad Graniewitz Visacovsky
Tamar Liron
Sahar Hiram-Bab
Michael Brines
Yankel Gabet
Drorit Neumann
Source :
International Journal of Molecular Sciences, Vol 23, Iss 1, p 55 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

The two erythropoietin (EPO) receptor forms mediate different cellular responses to erythropoietin. While hematopoiesis is mediated via the homodimeric EPO receptor (EPOR), tissue protection is conferred via a heteromer composed of EPOR and CD131. In the skeletal system, EPO stimulates osteoclast precursors and induces bone loss. However, the underlying molecular mechanisms are still elusive. Here, we evaluated the role of the heteromeric complex in bone metabolism in vivo and in vitro by using Cibinetide (CIB), a non-erythropoietic EPO analogue that exclusively binds the heteromeric receptor. CIB is administered either alone or in combination with EPO. One month of CIB treatment significantly increased the cortical (~5.8%) and trabecular (~5.2%) bone mineral density in C57BL/6J WT female mice. Similarly, administration of CIB for five consecutive days to female mice that concurrently received EPO on days one and four, reduced the number of osteoclast progenitors, defined by flow cytometry as Lin−CD11b−Ly6Chi CD115+, by 42.8% compared to treatment with EPO alone. In addition, CIB alone or in combination with EPO inhibited osteoclastogenesis in vitro. Our findings introduce CIB either as a stand-alone treatment, or in combination with EPO, as an appealing candidate for the treatment of the bone loss that accompanies EPO treatment.

Details

Language :
English
ISSN :
14220067 and 16616596
Volume :
23
Issue :
1
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.3792960f2764f709744bc7d33e8422f
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms23010055