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Blood and bones: osteoblastic HIF signaling regulates erythropoiesis.

Wu C, Rankin EB, Giaccia AJ - Cell Cycle (2012)

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ABSTRACT

Comment on: Rankin EB, et al. Cell 2012; 149:63-74.

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Figure 1. EPO production for the regulation of erythropoiesis occurs in the fetal liver and adult kidney. Rankin and Wu et al. demonstrate that manipulation of the PHD/VHL/HIF signaling pathway in osteoblasts elevates the erythroid lineage in the local hematopoietic environment and protects from anemia through modulation of EPO expression in bone. These findings implicate osteoblasts in bone as a novel source of endogenous EPO to stimulate erythropoiesis. The image depicts the regulation of erythropoiesis by an osteoblast with augmented HIF activity. Rankin and colleagues demonstrate that osteoblasts (shown attached to the bone surface) secrete EPO (green) which stimulates erythroid progenitor (purple) proliferation and differentiation in the bone marrow microenvironment. Artwork by Butch Colyear.
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Figure 1: Figure 1. EPO production for the regulation of erythropoiesis occurs in the fetal liver and adult kidney. Rankin and Wu et al. demonstrate that manipulation of the PHD/VHL/HIF signaling pathway in osteoblasts elevates the erythroid lineage in the local hematopoietic environment and protects from anemia through modulation of EPO expression in bone. These findings implicate osteoblasts in bone as a novel source of endogenous EPO to stimulate erythropoiesis. The image depicts the regulation of erythropoiesis by an osteoblast with augmented HIF activity. Rankin and colleagues demonstrate that osteoblasts (shown attached to the bone surface) secrete EPO (green) which stimulates erythroid progenitor (purple) proliferation and differentiation in the bone marrow microenvironment. Artwork by Butch Colyear.

Mentions: In Volume 149, Issue 1 of Cell, Rankin et al. discovered a previously unidentified source of endogenous Epo capable of stimulating erythropoiesis (Fig. 1). In their studies, a Cre-loxP approach was used to inactivate VHL and, thus, constitutively activate HIF signaling, specifically in cells of the osteoblastic lineage. Augmented HIF activity in osteoblasts resulted in enhanced erythropoiesis marked by the development of severe polycythemia by 8 weeks of age in 100% of mutant mice. The development of polycythemia occurred in an EPO-dependent manner and was associated with an increase in EPO expression in bone and decreased EPO expression in the kidney. Elevated bone EPO expression occurred in a HIF-2α-dependent manner, demonstrating that HIF-2α expression in osteoblasts drives EPO expression in bone. In the endogenous setting, Rankin et al. found that bone and primary osteoblasts cultures from neonatal mice also expressed Epo in a HIF-2α dependent manner. Studies investigating the endogenous role of EPO in bone are eagerly awaited, as homeostatic erythropoiesis was maintained in HIF-2α-deficient mice.


Blood and bones: osteoblastic HIF signaling regulates erythropoiesis.

Wu C, Rankin EB, Giaccia AJ - Cell Cycle (2012)

Figure 1. EPO production for the regulation of erythropoiesis occurs in the fetal liver and adult kidney. Rankin and Wu et al. demonstrate that manipulation of the PHD/VHL/HIF signaling pathway in osteoblasts elevates the erythroid lineage in the local hematopoietic environment and protects from anemia through modulation of EPO expression in bone. These findings implicate osteoblasts in bone as a novel source of endogenous EPO to stimulate erythropoiesis. The image depicts the regulation of erythropoiesis by an osteoblast with augmented HIF activity. Rankin and colleagues demonstrate that osteoblasts (shown attached to the bone surface) secrete EPO (green) which stimulates erythroid progenitor (purple) proliferation and differentiation in the bone marrow microenvironment. Artwork by Butch Colyear.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3383578&req=5

Figure 1: Figure 1. EPO production for the regulation of erythropoiesis occurs in the fetal liver and adult kidney. Rankin and Wu et al. demonstrate that manipulation of the PHD/VHL/HIF signaling pathway in osteoblasts elevates the erythroid lineage in the local hematopoietic environment and protects from anemia through modulation of EPO expression in bone. These findings implicate osteoblasts in bone as a novel source of endogenous EPO to stimulate erythropoiesis. The image depicts the regulation of erythropoiesis by an osteoblast with augmented HIF activity. Rankin and colleagues demonstrate that osteoblasts (shown attached to the bone surface) secrete EPO (green) which stimulates erythroid progenitor (purple) proliferation and differentiation in the bone marrow microenvironment. Artwork by Butch Colyear.
Mentions: In Volume 149, Issue 1 of Cell, Rankin et al. discovered a previously unidentified source of endogenous Epo capable of stimulating erythropoiesis (Fig. 1). In their studies, a Cre-loxP approach was used to inactivate VHL and, thus, constitutively activate HIF signaling, specifically in cells of the osteoblastic lineage. Augmented HIF activity in osteoblasts resulted in enhanced erythropoiesis marked by the development of severe polycythemia by 8 weeks of age in 100% of mutant mice. The development of polycythemia occurred in an EPO-dependent manner and was associated with an increase in EPO expression in bone and decreased EPO expression in the kidney. Elevated bone EPO expression occurred in a HIF-2α-dependent manner, demonstrating that HIF-2α expression in osteoblasts drives EPO expression in bone. In the endogenous setting, Rankin et al. found that bone and primary osteoblasts cultures from neonatal mice also expressed Epo in a HIF-2α dependent manner. Studies investigating the endogenous role of EPO in bone are eagerly awaited, as homeostatic erythropoiesis was maintained in HIF-2α-deficient mice.

View Article: PubMed Central - PubMed

ABSTRACT

Comment on: Rankin EB, et al. Cell 2012; 149:63-74.

Show MeSH
Related in: MedlinePlus