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

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 implicati...

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Published in:International journal of molecular sciences 2022-10, Vol.23 (19), p.12051
Main Authors: Awida, Zamzam, Hiram-Bab, Sahar, Bachar, Almog, Saed, Hussam, Zyc, Dan, Gorodov, Anton, Ben-Califa, Nathalie, Omari, Sewar, Omar, Jana, Younis, Liana, Iden, Jennifer Ana, Graniewitz Visacovsky, Liad, Gluzman, Ida, Liron, Tamar, Raphael-Mizrahi, Bitya, Kolomansky, Albert, Rauner, Martina, Wielockx, Ben, Gabet, Yankel, Neumann, Drorit
Format: Article
Language:English
Subjects:
Anemia
Animal models
Bone growth
Bone loss
Bone marrow
Bone mass
Bone resorption
Cytokines
Erythropoiesis
Erythropoietin
Females
Lymphocytes B
Monocytes
Osteogenesis
Rodents
Statistical analysis
Statistical significance
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms231912051