Skeleton-vasculature chain reaction: a novel insight into the mystery of homeostasis

Abstract

Angiogenesis and osteogenesis are coupled. However, the cellular and molecular regulation of these processes remains to be further investigated. Both tissues have recently been recognized as endocrine organs, which has stimulated research interest in the screening and functional identification of novel paracrine factors from both tissues. This review aims to elaborate on the novelty and significance of endocrine regulatory loops between bone and the vasculature. In addition, research progress related to the bone vasculature, vessel-related skeletal diseases, pathological conditions, and angiogenesis-targeted therapeutic strategies are also summarized. With respect to future perspectives, new techniques such as single-cell sequencing, which can be used to show the cellular diversity and plasticity of both tissues, are facilitating progress in this field. Moreover, extracellular vesicle-mediated nuclear acid communication deserves further investigation. In conclusion, a deeper understanding of the cellular and molecular regulation of angiogenesis and osteogenesis coupling may offer an opportunity to identify new therapeutic targets.

An up to date on clinical prospects and management of osteoarthritis

“…The most promising treatments are those that target articular cartilage molecular processes [ [156] , [157] , [158] ]. The development of new therapeutic options for OA will require better knowledge of the disease.…”

New Insights to the Crosstalk between Vascular and Bone Tissue in Chronic Kidney Disease–Mineral and Bone Disorder

“…The endothelial cells should be seen as an integral part of bone tissue as these cells secrete factors with significant effects on both modeling and remodeling of bone. As such, paracrine regulatory loops exit between angiokines and osteokines in the bone microcirculation [22,23].…”

“…In bone, it has been proposed that NO also functions as a regulator of osteoblast differentiation and a mechanoresponsive mediator in the endothelial-bone cell crosstalk [26][27][28][29][30]. Endothelial-derived prostaglandin has also been proposed to promote osteoblast differentiation [22,31,32]. Endothelin-1 is associated with proliferation and differentiation of osteoprogenitor cells in bone tissue [33].…”

“…The RANKL-RANK-OPG regulatory system is a fundamental part of bone homeostasis and represents osteoblast/osteocyte regulation of osteoclast activity [34,35]. Adding to the complexity of cell crosstalk in bone turnover, the endothelium also secretes RANKL and OPG, this is thought to regulate bone turnover in response to other stimuli such as inflammatory cytokines and vascular endothelial growth factor (VEGF) [22,36]. Bone morphogenetic protein 2 (BMP2) promotes bone formation and mineralization through a cascade of different cellular mechanisms during embryonic and post embryonic development [37].…”

“…In response to hypoxia or VEGF, the endothelial cells upregulate BMP2 expression and increase its secretion [38]. Another proposed important signal pathway is the Delta-like 4-Notch-Noggin, where noggin is secreted by the endothelial cells and promotes recruitment and differentiation of osteoprogenitor cells [22,39]. The endothelial pleiotrophin stimulates osteoblast recruitment and facilitates osteoblast attachment to the bone matrix [40].…”