Dai J, Rabie A B M
The Biomedical and Tissue Engineering Group, Department of Orthodontics, Faculty of Dentistry, The University of Hong Kong, 34 Hospital Road, Hong Kong SAR, China.
J Dent Res. 2007 Oct;86(10):937-50. doi: 10.1177/154405910708601006.
During bone growth, development, and remodeling, angiogenesis as well as osteogenesis are closely associated processes, sharing some essential mediators. Vascular endothelial growth factor (VEGF) was initially recognized as the best-characterized endothelial-specific growth factor, which increased vascular permeability and angiogenesis, and it is now apparent that this cytokine regulates multiple biological functions in the endochondral ossification of mandibular condylar growth, as well as long bone formation. The complexity of VEGF biology is paralleled by the emerging complexity of interactions between VEGF ligands and their receptors. This narrative review summarizes the family of VEGF-related molecules, including 7 mammalian members, namely, VEGF, placenta growth factor (PLGF), and VEGF-B, -C, -D, -E, and -F. The biological functions of VEGF are mediated by at least 3 corresponding receptors: VEGFR-1/Flt-1, VEGFR-2/Flk-1, VEGFR-3/Flt-4 and 2 co-receptors of neuropilin (NRP) and heparan sulfate proteoglycans (HSPGs). Current findings on endochondral ossification are also discussed, with emphasis on VEGF-A action in osteoblasts, chondroblasts, and chondroclasts/osteoclasts and regulatory mechanisms involving oxygen tension, and some growth factors and hormones. Furthermore, the therapeutic implications of recombinant VEGF-A protein therapy and VEGF-A gene therapy are evaluated. Abbreviations used: VEGF, Vascular endothelial growth factor; PLGF, placenta growth factor; NRP, neuropilin; HSPGs, heparan sulfate proteoglycans; FGF, fibroblast growth factor; TGF, transforming growth factor; HGF, hepatocyte growth factor; TNF, tumor necrosis factor; ECM, extracellular matrix; RTKs, receptor tyrosine kinases; ERK, extracellular signal kinases; HIF, hypoxia-inducible factor.
在骨骼生长、发育和重塑过程中，血管生成和成骨是密切相关的过程，共享一些关键介质。血管内皮生长因子（VEGF）最初被认为是特征最明确的内皮特异性生长因子，它可增加血管通透性和血管生成，现在很明显这种细胞因子在下颌髁突生长的软骨内成骨以及长骨形成中调节多种生物学功能。VEGF生物学的复杂性与VEGF配体及其受体之间相互作用的日益复杂相平行。这篇叙述性综述总结了VEGF相关分子家族，包括7个哺乳动物成员，即VEGF、胎盘生长因子（PLGF）以及VEGF-B、-C、-D、-E和-F。VEGF的生物学功能由至少3种相应受体介导：VEGFR-1/Flt-1、VEGFR-2/Flk-1、VEGFR-3/Flt-4以及神经纤毛蛋白（NRP）和硫酸乙酰肝素蛋白聚糖（HSPG）的2种共受体。还讨论了目前关于软骨内成骨的研究结果，重点是VEGF-A在成骨细胞、软骨细胞和成软骨细胞/破骨细胞中的作用以及涉及氧张力的调节机制，还有一些生长因子和激素。此外，评估了重组VEGF-A蛋白疗法和VEGF-A基因疗法的治疗意义。使用的缩写：VEGF，血管内皮生长因子；PLGF，胎盘生长因子；NRP，神经纤毛蛋白；HSPG，硫酸乙酰肝素蛋白聚糖；FGF，成纤维细胞生长因子；TGF，转化生长因子；HGF，肝细胞生长因子；TNF，肿瘤坏死因子；ECM，细胞外基质；RTK，受体酪氨酸激酶；ERK，细胞外信号激酶；HIF，缺氧诱导因子。
