Angiogenic–osteogenic coupling mediated by bidirectional cross talk between chondro-/osteoblast lineage cells and skeletal endothelial cells

Angiogenic–osteogenic coupling mediated by bidirectional cross talk between chondro-/osteoblast lineage cells and skeletal endothelial cells. Schematic view of the dynamic and reciprocal interplay between the different cell types in the bone environment that couples angiogenesis and osteogenesis. (Right and upper part) Previous work implicated the VHL–HIF–VEGF signaling pathway in the osteogenic compartment of the long bones as a key driver of angiogenic–osteogenic coupling by effecting both (i) cell autonomous roles in chondrocytes, osteoprogenitors and osteoblasts and (ii) VEGF-mediated paracrine effects on the blood vessels in the bone environment, stimulating angiogenesis (brown arrows and notifications). (Left and lower part) New work from the group of Ralf Adams (red in the scheme) identifies a specialized subtype of endothelial cells (ECs), constituting type H vessels in the metaphysis and endosteum. These ECs mediate the growth of the blood vessels in bone, through a tissue-selective mechanism of angiogenesis involving positive regulation by the VHL/HIF and Notch/Dll4 signaling pathways. Coupling of angiogenesis back to osteogenesis is mediated by osteo-regulatory signals produced by ECs (angiocrine, osteogenic signaling). Among the angiocrine signals released from H-type vessels, Noggin stood out as the candidate most influential in mediating the osteogenic effects; addition of recombinant Noggin rescued the abundance of perivascular osteoprogenitors, the growth plate abnormalities and the ossification defect in mice carrying EC-specific loss-of-function mutations in the Notch pathway.

Publication

Angiogenic–osteogenic coupling: the endothelial perspective. (2014) Christa Maes, et al. Bonekey Rep. 2014;3:578. Figure: F1. Drosophila melanogaster

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