Details

Autor(en) / Beteiligte

• Deshet-Unger, Naamit
• Kolomansky, Albert
• Ben-Califa, Nathalie
• Hiram-Bab, Sahar
• Gilboa, Dafna
• Liron, Tamar
• Ibrahim, Maria
• Awida, Zamzam
• Gorodov, Anton
• Oster, Howard S
• Mittelman, Moshe
• Rauner, Martina
• Wielockx, Ben
• Gabet, Yankel
• Neumann, Drorit

Titel

Erythropoietin receptor in B cells plays a role in bone remodeling in mice

Ist Teil von

• Theranostics, 2020-01, Vol.10 (19), p.8744-8756

Ort / Verlag

Australia: Ivyspring International Publisher Pty Ltd

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. We have combined specifically-designed experimental mouse models and based osteoclastogenesis assays, as well as PCR analysis of gene expression. (i) EPO treatment increased RANKL expression in bone marrow (BM) B cells, suggesting a paracrine effect on osteoclastogenesis; (ii) B cell-derived osteoclastogenesis occured and as demonstrated by B cell lineage tracing in murine models; (iii) B-cell-derived osteoclastogenesis 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. 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 .