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. 2013 Jul 10:4:85.
doi: 10.3389/fendo.2013.00085. eCollection 2013.

Regulation of Bone Marrow Angiogenesis by Osteoblasts during Bone Development and Homeostasis

Ernestina Schipani  1 , Collen Wu, Erinn B Rankin, Amato J Giaccia
Affiliations

Regulation of Bone Marrow Angiogenesis by Osteoblasts during Bone Development and Homeostasis

Ernestina Schipani et al. Front Endocrinol (Lausanne). .

Abstract

Bone marrow is a highly heterogeneous and vascularized tissue. The various cell types populating the bone marrow extensively communicate with each other, and cell-to-cell cross talk is likely to be essential for proper bone development and homeostasis. In particular, the existence of osteogenesis and angiogenesis coupling has been recently proposed. Despite its high degree of vascularization, a gradient of oxygenation is present in the bone marrow, and the endosteal surface of cortical bone appears to be among the most hypoxic areas in the body. Oxygen (O2) is both an essential metabolic substrate and a regulatory signal that is in charge of a specific genetic program. An important component of this program is the family of transcription factors known as hypoxia-inducible factors (HIFs). In this Perspective, we will summarize our current knowledge about the role of the HIF signaling pathway in controlling bone development and homeostasis, and especially in regulating the crosstalk between osteoblasts, progenitor cells, and bone marrow blood vessels.

Keywords: erythropoietin; hypoxia-inducible factor; osteoblasts; prolyl hydroxylases; vascular endothelial growth factor.

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Figures

Figure 1
Figure 1
Loss of VHL in cells of the osteoblast lineage increases trabecular bone mass. H and E of histological sections of tibia isolated from 4-month-old control (CNTRL) and OSX-VHL mutant (VHL) mice; bottom panels are blows up of a and b, respectively. For details, see Text.
Figure 2
Figure 2
Osteoblastic HIFs control bone marrow angiogenesis. Gradients of oxygenation are present in the bone marrow with osteoblasts at the endosteal surface of bone being among the most hypoxic areas. Osteoblasts express HIFs, which regulate osteoblast activity and angiogenesis. Some of the HIF effects on angiogenesis could be mediated by VEGF, EPO, and/or other proangiogenic factors. It has yet to be defined whether increased angiogenesis is a necessary pre-requisite for the high bone mass phenotype observed upon activation of HIFs in cells of the osteoblast lineage. OB, osteoblast; EC, endothelial cell.
See this image and copyright information in PMC

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