Abstract
Vascularization is fundamental for bone formation and bone tissue homeostasis. However, in human subjects, a direct molecular relationship has not been identified between angiogenesis and agents that promote bone disease or factors related to age. Osteopenia is a condition in which bone mineral density is lower than normal, and it represents a sign of normal aging. Here we tested whether the type H vessel, which was recently identified as strongly positive for CD31 and Endomucin (CD31hiEmcnhi) in mice, is an important indicator of aging and osteopenia in human subjects. We found that age-dependent losses of type H vessels in human bone sections conform to the observations in aged mice. The abundance of human type H vessels and osteoprogenitors may be relevant to changes in the skeletal microarchitecture and advanced osteopenia. Furthermore, ovariectomized mice, a widely used model for postmenopausal osteoporosis, exhibited significantly reduced type H vessels accompanied by reduced osteoprogenitors, which is consistent with impaired bone microarchitecture and osteoporosis, suggesting that this feature is an indicator of bone mass independent of aging. More importantly, administration of desferrioxamine led to significantly increased bone mass via enhanced angiogenesis and increased type H vessels in ovariectomized mice. Altogether, these data represent a novel finding that type H vessels are regulated in aged and osteopenia subjects. The abundance of human type H vessels is an early marker of bone loss and represents a potential target for improving bone quality via the induction of type H vessels.
Highlights
The loss of bone mass experienced by many postmenopausal women and elderly men has the potential to weaken bones and increase the likelihood of bone fracture and could lead to the onset of osteoporosis.[1]
Studies in recent years have greatly expanded our understanding of bone formation in mice, and research has been performed to evaluate osteoporosis associated with inflammatory states;[2,3] ATF4,4,5 WNT
Osteoprogenitor cells (Osterix+), which further differentiate into osteoblasts and osteocytes,[20] are located directly adjacent to type H vessels, which suggests that reprogramming endothelial cells into type H endothelial cells may be beneficial for the treatment of osteoporosis or the promotion of bone fracture healing
Summary
The loss of bone mass experienced by many postmenopausal women and elderly men has the potential to weaken bones and increase the likelihood of bone fracture and could lead to the onset of osteoporosis.[1]. Osteogenic coupling is crucial for bone homeostasis, and it is tightly regulated by a specific capillary subtype in bone that is known as a type H vessel in mice.[18] These type H vessels have been identified in specific locations, mainly in the metaphysis near the growth plate and in the endosteum. Considerable differences in Received 06.10.16; revised 25.12.16; accepted 11.1.17; Edited by Y Shi bone anatomy, macrostructure, and microstructure occur between mice and humans, and information on type H vessels in human subjects remains elusive It is unclear whether reductions in type H vessels are an independent effect of decreased bone mass or caused by age-related factors. Our results strongly suggest that human type H vessels are an early indicator of bone loss
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