Angiogenesis and marrow stromal cell fates: roles in bone strength

In vivo osteogenic responses to anabolic stimuli--whether pharmacological or mechanical--are invariably accompanied by neovascularization. Microvascular endothelial-mesenchymal interactions have emerged that provide mechanistic insight into the roles of angiogenesis in the osteoanabolic response; these interactions resemble the epithelial-mesenchymal signaling that controls tissue morphogenesis during prenatal development. Microvascular smooth muscle cells called pericytes function as multipotent mesenchymal progenitors that contribute to bone, fat, cartilage and smooth muscle formation throughout life. This abbreviated overview recounts progress made in the past decade that highlights the physiological contributions of angiogenesis to bone formation and bone strength. It highlights the need to support research that details the mechanisms whereby angiogenesis, metabolic milieu and mechanical stimuli interact to control marrow stromal cell fate during the postnatal developmental process of aging and the disease processes of musculoskeletal frailty.