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Bone Abstracts (2014) 3 W3.2 | DOI: 10.1530/boneabs.3.W3.2

ECTS2014 Workshops Blood supply in pathophysiology of bone (3 abstracts)

Vessel–tissue interactions in the skeletal system

Ralf Adams


Muenster, Germany.


Angiogenesis is the main process mediating the expansion of the blood vessel network during development, tissue regeneration or in pathological conditions such as cancer. The formation of new endothelial sprouts, a key step in the angiogenic growth program, involves the selection of endothelial tip cells, which lead new sprouts. Angiogenic sprouting is induced by tissue-derived signals such as vascular endothelial growth factor (VEGF), which activates signaling by endothelial receptor tyrosine kinases. However, this response is strongly modulated by intrinsic signaling interactions between endothelial cells, which involve the Notch pathway.

More recently, we found that blood vessel growth in bone involves a specialized, tissue-specific form of angiogenesis that is distinct from other organ systems. Notch signaling promotes endothelial cell proliferation and vascular growth in postnatal long bone, which is the opposite of the well-established function of Notch and its ligand Dll4 in the endothelium of other organs and tumors. We also found that Notch controls the release of angiocrine signals from the bone endothelium and thereby controls perivascular osteoprogenitor cells. Using a combination of inducible, cell type-specific mouse genetics and pharmacological approaches, we also discovered that endothelial hypoxia-inducible factor 1 (H1F1α) promotes angiogenesis in the postnatal skeletal system and thereby bone formation. The sum of these findings establish a molecular framework coupling angiogenesis, angiocrine signals, and osteogenesis through endothelial Notch and HIF signaling, which may prove significant for the development of future therapeutic applications.

Volume 3

European Calcified Tissue Society Congress 2014

Prague, Czech Republic
17 May 2014 - 20 May 2014

European Calcified Tissue Society 

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