Zhu Sipin, Bennett Samuel, Kuek Vincent, Xiang Chuan, Xu Huazi, Rosen Vicki, Xu Jiake
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
School of Biomedical Sciences, The University of Western Australia, Perth, WA 6009, Australia.
Theranostics. 2020 May 1;10(13):5957-5965. doi: 10.7150/thno.45422. eCollection 2020.
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.
血管是遍布全身的管道，通过运输细胞、氧气和营养物质来支持组织生长和内环境稳定。内皮细胞（ECs）形成血管内壁，与周细胞一起，通过产生称为血管生成素的旁分泌信号分子，对器官发育和组织内环境稳定至关重要。在骨骼系统中，ECs衍生的血管生成素与骨细胞释放的血管生成因子共同协调骨微环境的细胞间串扰以及血管生成与骨生成的耦合。虽然血管生成因子和骨骼血管的参与相对已得到充分证实，但ECs衍生的血管生成素对骨和软骨内环境稳定的影响正逐渐显现。在本综述中，我们调查了ECs衍生的血管生成素，它们由局部微环境和远端器官的内皮细胞释放，并作为骨骼生长和内环境稳定的特异性调节因子发挥作用。这些可能包括具有成骨特性的血管生成素，如刺猬因子、Notch、WNT、骨形态发生蛋白（BMP）、成纤维细胞生长因子（FGF）、胰岛素样生长因子（IGF）和血小板衍生生长因子（PDGF）。了解ECs衍生的血管生成素协调骨和软骨内环境稳定及发病机制的多种机制，是开发骨骼疾病治疗潜力的重要一步。
