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Notch activity key to the link between angiogenesis and osteogensis
DOI:10.1038/bonekey.2014.86
This group has shown linked regulation of osteogenesis and angiogenesis within the bone marrow is mediated by type H endothelial cells that express high levels of CD-31 and endomucin. In this study, they investigate the role of Notch signaling in the process of endothelial cell proliferation.
Knockout mice that had disrupted Notch signaling in their endothelial cell system showed significantly reduced vasculature within their bones. Osteogenesis was also inhibited, resulting in shortened long bones, a reduction in bone mass, chondrocyte defects and loss of trabecular bone, compared to wild-type mice.
These defects arose because the absence of Notch meant that endothelial cells did not release the required levels of Noggin. This was confirmed in experiments in which bone growth, mineralization, trabecular bone formation, maturation of chondrocytes and the numbers of osteoprogenitor cells were restored by administering recombinant Noggin to mice.
Editor’s comment: The authors demonstrate that, in CD31-high endomucin-high type H capillary cells, Notch signaling enhances Noggin secretion, which plays an important role in enhancing skeletal growth and mineralization. This is distinct from the effect of Notch/Dll4 signaling in endothelial cells of other organs, and may provide new therapeutic approach to enhance fracture healing or counteract impaired osteogenesis.
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