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  • Erythropoietin directly stimulates osteoclast precursors and induces bone loss.

Erythropoietin directly stimulates osteoclast precursors and induces bone loss.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2015-01-30)
Sahar Hiram-Bab, Tamar Liron, Naamit Deshet-Unger, Moshe Mittelman, Max Gassmann, Martina Rauner, Kristin Franke, Ben Wielockx, Drorit Neumann, Yankel Gabet
摘要

Erythropoietin (EPO) primarily regulates red blood cell formation, and EPO serum levels are increased on hypoxic stress (e.g., anemia and altitude). In addition to anemia, recent discoveries suggest new therapeutic indications for EPO, unrelated to erythropoiesis. We investigated the skeletal role of EPO using several models of overexpression (Tg6 mice) and EPO administration (intermittent/continuous, high/low doses) in adult C57Bl6 female mice. Using microcomputed tomography, histology, and serum markers, we found that EPO induced a 32%-61% trabecular bone loss caused by increased bone resorption (+60%-88% osteoclast number) and reduced bone formation rate (-19 to -74%; P < 0.05 throughout). EPO targeted the monocytic lineage by increasing the number of bone monocytes/macrophages, preosteoclasts, and mature osteoclasts. In contrast to the attenuated bone formation in vivo, EPO treatment in vitro did not inhibit osteoblast differentiation and activity, suggesting an indirect effect of EPO on osteoblasts. However, EPO had a direct effect on preosteoclasts by stimulating osteoclastogenesis in isolated cultures (+60%) via the Jak2 and PI3K pathways. In summary, our findings demonstrate that EPO negatively regulates bone mass and thus bears significant clinical implications for the potential management of patients with endogenously or therapeutically elevated EPO levels.

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Sigma-Aldrich
铼, powder, 99.995% trace metals basis
Sigma-Aldrich
铼, foil, thickness 0.25 mm, 99.98% trace metals basis
Sigma-Aldrich
凝血酶受体激动剂, ≥97% (HPLC)
Sigma-Aldrich
铼, powder, −100 mesh, ≥99.9% trace metals basis
铼, wire reel, 0.025m, diameter 1.0mm, annealed, 99.97%
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铼, wire reel, 0.1m, diameter 0.125mm, annealed, 99.97%
铼, wire reel, 0.1m, diameter 0.15mm, annealed, 99.97%
铼, wire reel, 0.1m, diameter 0.178mm, annealed, 99.97%
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铼, wire reel, 0.2m, diameter 0.125mm, annealed, 99.97%
铼, wire reel, 0.2m, diameter 0.15mm, annealed, 99.97%
铼, wire reel, 0.2m, diameter 0.178mm, annealed, 99.97%
铼, wire reel, 0.2m, diameter 0.25mm, annealed, 99.97%
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铼, wire reel, 0.5m, diameter 0.076mm, annealed, 99.97%
铼, wire reel, 0.5m, diameter 0.10mm, annealed, 99.97%
铼, wire reel, 0.5m, diameter 0.125mm, annealed, 99.97%