Unique bone marrow blood vessels couple angiogenesis and osteogenesis in bone homeostasis and diseases

Abstract

Blood vessels serve as a versatile transport system and play crucial roles in organ development, regeneration, and stem cell behavior. In the skeletal system, certain capillaries support perivascular stem cells or osteoprogenitor cells and thereby regulate bone formation. Recent studies reported that a specialized capillary subtype, termed type H vessels, is shown to couple angiogenesis and osteogenesis in rodents and humans. They can be distinguished by specific cell surface markers, as the endothelial cells in the metaphysis and endosteum highly express the junctional protein CD31 and the sialoglycoprotein endomucin. Here, we provide an overview of the role of type H vessels in bone homeostasis and summarize their linkage with various cytokines to control bone cell behavior and bone formation. We also discuss the potential clinical application for bone disorders by targeting these specific vessels according to their physiological and pathobiological settings.

Genetic Scores of eNOS, ACE and VEGFA Genes Are Predictive of Endothelial Dysfunction Associated Osteoporosis in Postmenopausal Women

“…This is consistent with the finding that women suffering coronary endothelial dysfunction are at higher risk of developing osteoporosis than their normal counterparts [1]. Furthermore, substantial supply of blood to the bone reassures bone remodeling [11], creates a suitable microenvironment for growth factors and metabolites in fractured bone [9], reduces inflammation for bone healing [12] and couples osteogenesis and angiogenesis in bone homeostasis [13]. Alluding to these findings, it is evident that a clinically viable link exists between hormone levels, osteoporosis and endothelial dysfunction.…”

Microenvironment in subchondral bone: predominant regulator for the treatment of osteoarthritis

“…[46][47][48] Evidence has shown that the crosstalk between osteoblast or osteoclast lineage cells and type H ECs promotes subchondral angiogenesis and aggravates subchondral bone remodelling. [49][50][51] Type H ECs surrounded by osterix-expressing osteoprogenitors produce high levels of angiocrine factors (such as plateletderived growth factor (PDGF)-A, TGF-β1 and fibroblast growth factor (FGF)−1), stimulating survival, proliferation and differentiation of these osteoprogenitors to promote local bone formation. 52 53 Type H ECs intercommunicate via the intercellular Notch/delta-like protein 4 (DLL4) signalling pathway to induce the production of Noggin, 54 which stimulates the differentiation of osteoprogenitors surrounding vessels.…”

Biallelic mutations in LAMA5 disrupts a skeletal noncanonical focal adhesion pathway and produces a distinct bent bone dysplasia

“…Type H vessels are a specialized subtype of capillary that expresses high levels of CD31 and endomucin, and these vessels are located near the growth plate in the metaphysis, the periosteum, and the endosteum of the diaphysis. Type H vessels are densely surrounded by osteoprogenitors [39] and aid in modulating osteoblasts, coupling osteogenesis to angiogenesis. There is also an embryonically expressed vessel termed Type E, with a similar expression pattern to type H vessels, but in mice they are highly expressed at E16.5 and then exhibit diminished expression by P28 [19] .…”