Endothelial cells produce angiocrine factors to regulate bone and cartilage via versatile mechanisms

Blood vessels are conduits distributed throughout the body, supporting tissue growth and homeostasis by the transport of cells, oxygen and nutrients. Endothelial cells (ECs) form the linings of the blood vessels, and together with pericytes, are essential for organ development and tissue homeostasis through producing paracrine signalling molecules, called angiocrine factors. In the skeletal system, ECs - derived angiocrine factors, combined with bone cells-released angiogenic factors, orchestrate intercellular crosstalk of the bone microenvironment, and the coupling of angiogenesis-to-osteogenesis. Whilst the involvement of angiogenic factors and the blood vessels of the skeleton is relatively well established, the impact of ECs -derived angiocrine factors on bone and cartilage homeostasis is gradually emerging. In this review, we survey ECs - derived angiocrine factors, which are released by endothelial cells of the local microenvironment and by distal organs, and act specifically as regulators of skeletal growth and homeostasis. These may potentially include angiocrine factors with osteogenic property, such as Hedgehog, Notch, WNT, bone morphogenetic protein (BMP), fibroblast growth factor (FGF), insulin-like growth factor (IGF), and platelet-derived growth factor (PDGF). Understanding the versatile mechanisms by which ECs-derived angiocrine factors orchestrate bone and cartilage homeostasis, and pathogenesis, is an important step towards the development of therapeutic potential for skeletal diseases.