Human type H vessels are a sensitive biomarker of bone mass

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.

Nuciferine prevents bone loss by disrupting multinucleated osteoclast formation and promoting type H vessel formation

“…Angiogenesis plays an important role in sustaining the normal bone structure, and osteogenesis is based on the nutrient supply of blood vessels and requires molecular stimulation from endothelial cells . The contribution of type H vessels to bone formation has been verified, and its quantity is relevant to bone mass . Although we proved that NCF could inhibit osteoclast formation and increase the quantity of Trap + preosteoclasts, the influence of NCF on the function of endothelial cells and the formation of type H vessels was not clear.…”

H‐type blood vessels participate in alveolar bone remodeling during murine tooth extraction healing

“…The vasculature not only supplies the essential nutrients for bone remodeling (Carmeliet, 2005; Filipowska, Tomaszewski, Niedzwiedzki, Walocha, & Niedzwiedzki, 2017; Saran, Gemini Piperni, & Chatterjee, 2014; Stegen, Gastel, & Carmeliet, 2015), a newly discovered capillary subtype with high expression of CD31 and Endomucin (Emcn) (termed CD31 hi Emcn hi , H‐type blood vessels) also maintains perivascular osteoprogenitors and induces mesenchymal stem cell osteogenic differentiation by secreting paracrine molecules in mouse long bones (Kusumbe, Ramasamy, & Adams, 2014; Langen et al, 2017; Xie et al, 2014; Yang et al, 2017). The abundance of CD31 hi Emcn hi endothelial cells (H‐ECs) greatly declines in aged mouse and human long bones (Wang et al, 2017; Zhu et al, 2019), parallel with the age‐related osteoporosis. However, little is reported regarding the existence of H‐type vessels in alveolar bone, nor their roles in alveolar bone remodeling.…”

Endothelial ZEB1 promotes angiogenesis-dependent bone formation and reverses osteoporosis

“…CD31 hi EMCN hi vessels, residing in the bone marrow near the growth plate, represent the key component of a metabolically specialized bone microenvironment with privileged access to nutrients and oxygen, thereby promoting the growth potential of surrounding perivascular cells, including pre-osteoprogenitors, osteoprogenitors, mature osteoblasts, mature and hypertrophic chondrocytes, and hematopoietic stem cells [1][2][3][4][5] . It is increasingly appreciated that skeletal CD31 hi EMCN hi vessel numbers decline in ageing and ovariectomy (OVX)-induced osteoporotic mice and in osteoporotic patients 1,4,[6][7][8][9] . Osteoporosis is a systemic bone disease characterized by abnormal bone metabolism, low bone mass and density, impaired bone microstructure, and increased bone fragility and fracture prone [6][7][8][9] .…”

“…It is increasingly appreciated that skeletal CD31 hi EMCN hi vessel numbers decline in ageing and ovariectomy (OVX)-induced osteoporotic mice and in osteoporotic patients 1,4,[6][7][8][9] . Osteoporosis is a systemic bone disease characterized by abnormal bone metabolism, low bone mass and density, impaired bone microstructure, and increased bone fragility and fracture prone [6][7][8][9] . Reduced CD31 hi EMCN hi endothelium levels in the bone are strongly associated with osteoporosis progression.…”