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Open AccessArticle

Erythropoietin-Induced Changes in Bone and Bone Marrow in Mouse Models of Diet-Induced Obesity

Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20814, USA
*
Author to whom correspondence should be addressed.
Current address: Division of Endocrinology, Department of Medicine, Indiana University School of Medicine, R3-C110 ENDC, Indiana University, Indianapolis, IN 46202, USA.
Int. J. Mol. Sci. 2020, 21(5), 1657; https://doi.org/10.3390/ijms21051657
Received: 29 January 2020 / Revised: 18 February 2020 / Accepted: 26 February 2020 / Published: 28 February 2020
(This article belongs to the Special Issue Erythropoietin)
Obesity remodels bone and increases bone marrow adipocytes (BMAT), which negatively regulate hematopoiesis and bone. Reduced BMAT could restore altered hematopoiesis and bone features. We analyzed the potential of erythropoietin (EPO), the cytokine required for erythropoiesis, to inhibit BMAT in C57BL6/J mice fed four weeks of a high-fat diet (HFD). Acute EPO administration markedly decreased BMAT in regular chow diet (RCD) and HFD-fed mice, without affecting whole body fat mass. Micro-CT analysis showed EPO reduced trabecular bone in RCD- and HFD-fed mice, but EPO-treated HFD-fed mice maintained cortical bone mineral density and cortical bone volume, which was reduced on RCD. Despite achieving similar increased hematocrits with BMAT loss in RCD- and HFD-fed mice treated with EPO, decreased bone marrow cellularity was only observed in RCD-fed mice concomitant with an increasing percentage of bone marrow erythroid cells. In contrast, in HFD-fed mice, EPO increased endothelial cells and stromal progenitors with a trend toward the normalization of marrow homeostasis. EPO administration increased c-terminal FGF23 and intact serum FGF23 only in HFD-fed mice. These data demonstrate the distinct EPO responses of bone and marrow in normal and obese states, accompanying EPO-induced loss of BMAT. View Full-Text
Keywords: erythropoietin; obesity; bone; bone marrow adipocyte; osteocyte; osteoblast; osteoclast; stromal cells; FGF23 erythropoietin; obesity; bone; bone marrow adipocyte; osteocyte; osteoblast; osteoclast; stromal cells; FGF23
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MDPI and ACS Style

Suresh, S.; Alvarez, J.C.; Dey, S.; Noguchi, C.T. Erythropoietin-Induced Changes in Bone and Bone Marrow in Mouse Models of Diet-Induced Obesity. Int. J. Mol. Sci. 2020, 21, 1657. https://doi.org/10.3390/ijms21051657

AMA Style

Suresh S, Alvarez JC, Dey S, Noguchi CT. Erythropoietin-Induced Changes in Bone and Bone Marrow in Mouse Models of Diet-Induced Obesity. International Journal of Molecular Sciences. 2020; 21(5):1657. https://doi.org/10.3390/ijms21051657

Chicago/Turabian Style

Suresh, Sukanya; Alvarez, Josue C.; Dey, Soumyadeep; Noguchi, Constance T. 2020. "Erythropoietin-Induced Changes in Bone and Bone Marrow in Mouse Models of Diet-Induced Obesity" Int. J. Mol. Sci. 21, no. 5: 1657. https://doi.org/10.3390/ijms21051657

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