Blood vessels define the properties of local microenvironments in the skeletal system, play crucial roles in osteogenesis and provide niches for haematopoietic stem cells. The properties of niche-forming vessels and their changes in the ageing organism remain incompletely understood. We have previously identified a new capillary subtype in the murine skeletal system with distinct morphological, molecular and functional properties. These vessels are CD31hi/Emcnhi, localized to growth plate and endosteal region, mediate growth of the bone vasculature, generate distinct metabolic and molecular microenvironments, maintain perivascular osteoprogenitors, and couple angiogenesis to osteogenesis. The abundance of these vessels and associated osteoprogenitors was strongly reduced in bone from aged animals, which was pharmacologically reversible to restore bone mass. Here, we show that Notch signalling in endothelial cells leads to the expansion of haematopoietic stem cell niches in bone. While endothelial hypoxia-inducible factor signalling promotes neo-angiogenesis, it fails to induce arterialization and expansion of PDGFRβ-positive perivascular cells and thereby does not improve vascular niche function. In ageing mice, niche-forming vessels in the skeletal system are strongly reduced but can be restored by activation of Notch signalling in endothelial cells. These findings argue that vascular niches are part of complex, age-dependent microenvironments involving multiple cell populations and vessel subtypes.
14 May 2016 - 17 May 2016