Blood Vessels and Vascular Niches in Bone Development and Physiological Remodeling

Abstract

Recent advances in our understanding of blood vessels and vascular niches in bone convey their critical importance in regulating bone development and physiology. The contribution of blood vessels in bone functions and remodeling has recently gained enormous interest because of their therapeutic potential. The mammalian skeletal system performs multiple functions in the body to regulate growth, homeostasis and metabolism. Blood vessels provide support to various cell types in bone and maintain functional niches in the bone marrow microenvironment. Heterogeneity within blood vessels and niches indicate the importance of specialized vascular niches in regulating skeletal functions. In this review, we discuss physiology of bone vasculature and their specialized niches for hematopoietic stem cells and mesenchymal progenitor cells. We provide clinical and experimental information available on blood vessels during physiological bone remodeling.

Microbiota-Derived Metabolites, Indole-3-aldehyde and Indole-3-acetic Acid, Differentially Modulate Innate Cytokines and Stromal Remodeling Processes Associated with Autoimmune Arthritis

“…In addition, a time-dependent interplay between IAld and I3AA concomitant treatment was observed. These findings highlight the potentially differential outcomes in arthritic severity depending on the relative levels of these two indole-derivates by acting at different stages of blood vessel formation [ 54 ]. Additionally, we observed that CH-223191 failed to suppress the pro-angiogenic effect of IAld but the anti-angiogenic effect of I3AA was reversed by CH-223191.…”

Infectious Osteomyelitis: Marrying Bone Biology and Microbiology to Shed New Light on a Persistent Clinical Challenge

“…In terms of bone vasculature, large blood vessels enter through the cortex mid‐shaft in larger bones, branching toward the metaphyses and along endosteum, where type H capillaries are found, and into the marrow, which holds a highly branched sinusoidal network of type L vessels. ( 66 ) Oxygen levels are higher in the areas fed by type H vessels than type L, and the endothelium of these vessels differs as well. The differing oxygenation of these microenvironments may dictate localization and proliferation of pathogens with different tolerance of oxygen (ie, facultative versus strict anaerobic bacteria), but this has not been directly tested yet.…”

“…Finally, the organization of blood vessels and nerve fibers, which often run together, at least through cortical bone, varies substantially both within and across bones. ( 66–69 ) In addition to providing openings in the bone matrix through which microbes can travel, both neural and vascular cells can interact with host and pathogen. In terms of bone vasculature, large blood vessels enter through the cortex mid‐shaft in larger bones, branching toward the metaphyses and along endosteum, where type H capillaries are found, and into the marrow, which holds a highly branched sinusoidal network of type L vessels.…”

Accelerated Bone Regeneration by Adrenomedullin 2 Through Improving the Coupling of Osteogenesis and Angiogenesis via β-Catenin Signaling

“…The skeleton is a highly vascularized tissue containing an abundant capillary network, which not only provides access to nutrients and oxygen, but also secretes various cytokines, regulating the local osteogenic microenvironment (Stegen et al, 2015;Ramasamy et al, 2016;Hendriks and Ramasamy, 2020;Stucker et al, 2020). Kusumbe defined type-H endothelial cells, which exhibit important functions in the regulation of osteogenesis and angiogenesis, based on the criterion of a high expression of platelet endothelial cell adhesion molecule-1 and endomucin (CD31 hi EMCN hi ) (Kusumbe et al, 2014).…”