Erythropoietin Receptor (EPOR) Signaling in the Osteoclast Lineage Contributes to EPO-Induced Bone Loss in Mice

Zamzam Awida, Sahar Hiram-Bab, Almog Bachar, Hussam Saed, Dan Zyc, Anton Gorodov, Nathalie Ben-Califa, Sewar Omari, Jana Omar, Liana Younis, Jennifer Ana Iden, Liad Graniewitz Visacovsky, Ida Gluzman, Tamar Liron, Bitya Raphael-Mizrahi, Albert Kolomansky, Martina Rauner, Ben Wielockx, Yankel Gabet, Drorit Neumann*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Erythropoietin (EPO) is a pleiotropic cytokine that classically drives erythropoiesis but can also induce bone loss by decreasing bone formation and increasing resorption. Deletion of the EPO receptor (EPOR) on osteoblasts or B cells partially mitigates the skeletal effects of EPO, thereby implicating a contribution by EPOR on other cell lineages. This study was designed to define the role of monocyte EPOR in EPO-mediated bone loss, by using two mouse lines with conditional deletion of EPOR in the monocytic lineage. Low-dose EPO attenuated the reduction in bone volume (BV/TV) in Cx3cr1Cre EPORf/f female mice (27.05%) compared to controls (39.26%), but the difference was not statistically significant. To validate these findings, we increased the EPO dose in LysMCre model mice, a model more commonly used to target preosteoclasts. There was a significant reduction in both the increase in the proportion of bone marrow preosteoclasts (CD115+) observed following high-dose EPO administration and the resulting bone loss in LysMCre EPORf/f female mice (44.46% reduction in BV/TV) as compared to controls (77.28%), without interference with the erythropoietic activity. Our data suggest that EPOR in the monocytic lineage is at least partially responsible for driving the effect of EPO on bone mass.

Original languageEnglish
Article number12051
JournalInternational Journal of Molecular Sciences
Volume23
Issue number19
DOIs
StatePublished - Oct 2022

Funding

FundersFunder number
Cancer Biology Research Center
Dotan Hemato-oncology Fund
German-Israel FoundationI-1433-203.12/2017
Israel Science Foundation1086/17, 1188/21
Tel Aviv University

    Keywords

    • CD115
    • bone
    • erythropoietin (EPO)
    • erythropoietin receptor (EPOR)
    • osteoclasts

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