Vascular Endothelial Growth Factor: An Essential Component of Angiogenesis and Fracture Healing

Abstract

Fractures require adequate stability and blood supply to heal. The vascular supply to long bones is compromised in a fracture, and the ability to heal hinges on the ability of new blood vessels to proliferate from surrounding vessels in a process known as angiogenesis. This process is largely driven by the growth factor, vascular endothelial growth factor (VEGF), whose levels are increased locally and systemically during fracture healing. VEGF is involved in many steps throughout the fracture healing cascade, from initially being concentrated in fracture hematoma, to the promotion of bone turnover during the final remodeling phase. This article reviews the current literature surrounding the role of VEGF and other growth factors in reestablishing vascular supply to fractured bone, as well as medications and surgical techniques that may inhibit this process.

The potential role of VEGF-induced vascularisation in the bony repair of injured growth plate cartilage

“…Angiogenesis is important for providing oxygen, vital nutrients and cells essential for successful bone development, growth as well as fracture repair (Carano & Filvaroff 2003, Keramaris et al 2008, Tang et al 2012. Although fibroblast growth factor 2, platelet-derived growth factor (PDGFBB) and vascular endothelial growth factor (VEGF) have all been associated as angiogenic growth factors, VEGF has been identified as the key mediator for angiogenesis (Ogden 2000a,b,c, Keramaris et al 2008, Beamer et al 2010. In addition to VEGF's roles in the migration and proliferation of endothelial cells and blood vessel formation (Carlevaro et al 2000), VEGF receptors have also been localised on osteoblasts (Midy & Plouet 1994, Deckers et al 2000 and osteoclasts (Nakagawa et al 2000, Street et al 2002 -indicating the potential importance of VEGF in both angiogenesis as well as osteogenesis and bone remodelling.…”

Whole extracts of Radix Achyranthis Bidentatae and Radix Cyathulae promote angiogenesis in human umbilical vein endothelial cells in vitro and in zebrafish in vivo

“…In the treatments of these diseases, the role of angiogenesis has been demonstrated in numerous scientific reports (3)(4)(5). For example, physiological angiogenesis always occurs in the endometrium during the menstrual cycle, and appears in the basalis layer during menstruation and in the functionalis and subepithelial capillary plexus during the proliferative and early secretory stages (3).…”

“…Normal physiological angiogenesis is rarely observed in adults except in the ovary and endometrium during females' reproductive life (3). In numerous pathological conditions, angiogenesis is also required to facilitate tissue repair by transferring more nutrients and oxygen to the ischemia sites, which is beneficial to treat several types of illnesses, including myocardial ischemia, osteonecrosis, bone fracture and ischemic chronic wounds such as a diabetic limb (4)(5)(6).…”

“…As suggested by the Chinese pharmacopoeia, β-ecdysterone is one of the major bioactive markers in the RAB extract, and cyasterone is found as an authentic standard in the RC extract (7,10,11). Although there is no direct concept on angiogenesis in the principles of TCM, RAB and RC are traditionally applied with the aim of stimulating menstruation and curing bone diseases in which angiogenesis is critical (3)(4)(5). The aim of the present study was to explore whether the whole extracts of RAB and RC both possess potential pro-angiogenic effects, which may indicate the pharmacological mechanism underlying their hypothesized traditional therapeutic effects.…”

Comparison of Angiogenesis in Bone Defect Healing Process due to the Difference in the Frequency of Low-Intensity Pulsed Ultrasound (LIPUS)

“…Furthermore, LIPUS exposure group had higher new capirally vessel formation ratio in all layer of bone defected area at 7 days than control group (p < 0.05, data not shown). VEGF known as a key growth factor directly associated with angiogenesis and neovascularization is produced by endothelial cells, macrophages, fibroblast, smooth muscle cells and osteoblasts 22) . Some studies reported VEGF expression was upregulated by LIUPS exposure.…”