@article{099e5975d825476b9e62c3bf8c940932,
title = "Erythropoietin receptor in B cells plays a role in bone remodeling in mice",
abstract = "Erythropoietin (EPO) is a key regulator of erythropoiesis. However, EPO receptors (EPO-Rs) are also expressed on non-erythroid cell types, including myeloid and bone cells. Immune cells also participate in bone homeostasis. B cells produce receptor activator of nuclear factor kappa-Β ligand (RANKL) and osteoprotegerin (OPG), two pivotal regulators of bone metabolism. Here we explored the ability of B cells to transdifferentiate into functional osteoclasts and examined the role of EPO in this process in a murine model. Methods: We have combined specifically-designed experimental mouse models and in vitro based osteoclastogenesis assays, as well as PCR analysis of gene expression. Results: (i) EPO treatment in vivo increased RANKL expression in bone marrow (BM) B cells, suggesting a paracrine effect on osteoclastogenesis; (ii) B cell-derived osteoclastogenesis occured in vivo and in vitro, as demonstrated by B cell lineage tracing in murine models; (iii) B-cell-derived osteoclastogenesis in vitro was restricted to Pro-B cells expressing CD115/CSF1-R and is enhanced by EPO; (iv) EPO treatment increased the number of B-cell-derived preosteoclasts (β3+CD115+), suggesting a physiological rationale for B cell derived osteoclastogenesis; (v) finally, mice with conditional EPO-R knockdown in the B cell lineage (cKD) displayed a higher cortical and trabecular bone mass. Moreover, cKD displayed attenuated EPO-driven trabecular bone loss, an effect that was observed despite the fact that cKD mice attained higher hemoglobin levels following EPO treatment. Conclusions: Our work highlights B cells as an important extra-erythropoietic target of EPO-EPO-R signaling and suggests their involvement in the regulation of bone homeostasis and possibly in EPO-stimulated erythropoietic response. Importantly, we present here for the first time, histological evidence for B cell-derived osteoclastogenesis in vivo.",
keywords = "Bone marrow, CFMS/CD115/CSF1R, Erythropoietin, Lymphocytes, Osteoclastogenesis, Pro-B cells, Transdifferentiation",
author = "Naamit Deshet-Unger and Albert Kolomansky and Nathalie Ben-Califa and Sahar Hiram-Bab and Dafna Gilboa and Tamar Liron and Maria Ibrahim and Zamzam Awida and Anton Gorodov and Oster, {Howard S.} and Moshe Mittelman and Martina Rauner and Ben Wielockx and Yankel Gabet and Drorit Neumann",
note = "Publisher Copyright: {\textcopyright} The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.",
year = "2020",
doi = "10.7150/thno.45845",
language = "אנגלית",
volume = "10",
pages = "8744--8756",
journal = "Theranostics",
issn = "1838-7640",
publisher = "Ivyspring International Publisher",
number = "19",
}