TY - JOUR
T1 - Erythropoietin Receptor (EPOR) Signaling in the Osteoclast Lineage Contributes to EPO-Induced Bone Loss in Mice
AU - Awida, Zamzam
AU - Hiram-Bab, Sahar
AU - Bachar, Almog
AU - Saed, Hussam
AU - Zyc, Dan
AU - Gorodov, Anton
AU - Ben-Califa, Nathalie
AU - Omari, Sewar
AU - Omar, Jana
AU - Younis, Liana
AU - Iden, Jennifer Ana
AU - Graniewitz Visacovsky, Liad
AU - Gluzman, Ida
AU - Liron, Tamar
AU - Raphael-Mizrahi, Bitya
AU - Kolomansky, Albert
AU - Rauner, Martina
AU - Wielockx, Ben
AU - Gabet, Yankel
AU - Neumann, Drorit
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/10
Y1 - 2022/10
N2 - 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.
AB - 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.
KW - CD115
KW - bone
KW - erythropoietin (EPO)
KW - erythropoietin receptor (EPOR)
KW - osteoclasts
UR - http://www.scopus.com/inward/record.url?scp=85139949176&partnerID=8YFLogxK
U2 - 10.3390/ijms231912051
DO - 10.3390/ijms231912051
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 36233351
AN - SCOPUS:85139949176
SN - 1661-6596
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 19
M1 - 12051
ER -