Vascular endothelial growth factor: An essential component of angiogenesis and fracture healing

HSS Journal

Volumn 6, Issue 1, 2010, Pages 85-94

  Beamer, Brandon ^a   Hettrich, Carolyn ^b   Lane, Joseph ^b  

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

^b HOSPITAL FOR SPECIAL SURGERY   (United States)

Author keywords

Angiogenesis; Blood supply; Fracture; Fracture healing; Growth factor; Non union; Vascular endothelial growth factor; VEGF

Indexed keywords

EID: 76649119775     PISSN: 15563316     EISSN: 15563324     Source Type: Journal    
DOI: 10.1007/s11420-009-9129-4     Document Type: Review

References (66)

1. Boden SD, Einhorn TA, Morgan TS et al (2005) An AOA critical issue. The future of the orthopaedic surgeon-proceduralist or keeper of the musculoskeletal system? J. Bone Joint Surg. Am. 87(12): 2812-2821.
2. Glowacki J, Angiogenesis in fracture repair. Clin. Orthop. Relat. Res. 1998; (355 Suppl): S82-S89.
3. Brighton CT, Lorich DG, Kupcha R et al (1992) The pericyte as a possible osteoblast progenitor cell. Clin. Orthop. Relat. Res. 275: 287-299.
4. Testa U, Pannitteri G, Condorelli GL (2008) Vascular endothelial growth factors in cardiovascular medicine. J. Cardiovasc. Med. (Hagerstown) 9(12): 1190-1221.
5. Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat. Med. 9(6): 669-676.
6. Josko J, Gwozdz B, Jedrzejowska-Szypulka H et al (2000) Vascular endothelial growth factor (VEGF) and its effect on angiogenesis. Med. Sci. Monit. 6(5): 1047-1052.
7. Bluteau G, Julien M, Magne D et al (2007) VEGF and VEGF receptors are differentially expressed in chondrocytes. Bone 40(3): 568-576.
8. Deckers MM, van Bezooijen RL, van der Horst G et al (2002) Bone morphogenetic proteins stimulate angiogenesis through osteoblast-derived vascular endothelial growth factor A. Endocrinology 143(4): 1545-1553.
9. Mayr-Wohlfart U, Waltenberger J, Hausser H et al (2002) Vascular endothelial growth factor stimulates chemotactic migration of primary human osteoblasts. Bone 30(3): 472-477.
10. Wang DS, Miura M, Demura H et al (1997) Anabolic effects of 1, 25-dihydroxyvitamin D3 on osteoblasts are enhanced by vascular endothelial growth factor produced by osteoblasts and by growth factors produced by endothelial cells. Endocrinology 138(7): 2953-2962.
11. Mishima Y, Lotz M (2008) Chemotaxis of human articular chondrocytes and mesenchymal stem cells. J. Orthop. Res. 26(10): 1407-1412.
12. Lienau J, Schmidt-Bleek K, Peters A, et al., Differential regulation of blood vessel formation between standard and delayed bone healing. J. Orthop. Res. 2009.
13. Sarahrudi K, Thomas A, Braunsteiner T, et al., VEGF serum concentrations in patients with long bone fractures: A comparison between impaired and normal fracture healing. J. Orthop. Res. 2009.
14. Kawaguchi H, Kurokawa T, Hanada K et al (1994) Stimulation of fracture repair by recombinant human basic fibroblast growth factor in normal and streptozotocin-diabetic rats. Endocrinology 135(2): 774-781.
15. Carano RA, Filvaroff EH (2003) Angiogenesis and bone repair. Drug Discov. Today 8(21): 980-989.
16. Weiss S, Zimmermann G, Pufe T, et al., The systemic angiogenic response during bone healing. Arch. Orthop. Trauma Surg. 2008; 129: 989-997.
17. Ryaby JT, Sheller MR, Levine BP et al (2006) Thrombin peptide TP508 stimulates cellular events leading to angiogenesis, revascularization, and repair of dermal and musculoskeletal tissues. J. Bone Joint Surg. Am. 88(Suppl 3): 132-139.
18. Gerber HP, Ferrara N (2000) Angiogenesis and bone growth. Trends Cardiovasc. Med. 10(5): 223-228.
19. Harada S, Nagy JA, Sullivan KA et al (1994) Induction of vascular endothelial growth factor expression by prostaglandin E2 and E1 in osteoblasts. J. Clin. Invest. 93(6): 2490-2496.
20. Weiss S, Baumgart R, Jochum M et al (2002) Systemic regulation of distraction osteogenesis: a cascade of biochemical factors. J. Bone Miner. Res. 17(7): 1280-1289.
21. Weiss S, Zimmermann G, Baumgart R et al (2005) Systemic regulation of angiogenesis and matrix degradation in bone regeneration-distraction osteogenesis compared to rigid fracture healing. Bone 37(6): 781-790.
22. Manabe T, Mori S, Mashiba T et al (2007) Human parathyroid hormone (1-34) accelerates natural fracture healing process in the femoral osteotomy model of cynomolgus monkeys. Bone 40(6): 1475-1482.
23. Holstein JH, Menger MD, Scheuer C et al (2007) Erythropoietin (EPO): EPO-receptor signaling improves early endochondral ossification and mechanical strength in fracture healing. Life Sci. 80(10): 893-900.
24. Simpson AH, Mills L, Noble B (2006) The role of growth factors and related agents in accelerating fracture healing. J. Bone Joint Surg. Br. 88(6): 701-705.
25. Sena K, Sumner DR, Virdi AS (2007) Modulation of VEGF expression in rat bone marrow stromal cells by GDF-5. Connect. Tissue Res. 48(6): 324-331.
26. Reher P, Doan N, Bradnock B et al (1999) Effect of ultrasound on the production of IL-8, basic FGF and VEGF. Cytokine 11(6): 416-423.
27. Reed AA, Joyner CJ, Brownlow HC et al (2002) Human atrophic fracture non-unions are not avascular. J. Orthop. Res. 20(3): 593-599.
28. Einhorn TA (2005) The science of fracture healing. J. Orthop. Trauma 19(10 Suppl): S4-S6.
29. Phillips AM (2005) Overview of the fracture healing cascade. Injury 36(Suppl 3): S5-S7.
30. Street J, Winter D, Wang JH et al (2000) Is human fracture hematoma inherently angiogenic? Clin. Orthop. Relat. Res. 378: 224-237.
31. Brighton CT, Krebs AG (1972) Oxygen tension of nonunion of fractured femurs in the rabbit. Surg. Gynecol. Obstet. 135(3): 379-385.
32. Semenza GL, Wang GL (1992) A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol. Cell Biol. 12(12): 5447-5454.
33. Komatsu DE, Hadjiargyrou M (2004) Activation of the transcription factor HIF-1 and its target genes, VEGF, HO-1, iNOS, during fracture repair. Bone 34(4): 680-688.
34. Eckardt H, Ding M, Lind M et al (2005) Recombinant human vascular endothelial growth factor enhances bone healing in an experimental nonunion model. J. Bone Joint. Surg. Br. 87(10): 1434-1438.
35. Street J, Bao M, deGuzman L et al (2002) Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc. Natl. Acad. Sci. U. S. A. 99(15): 9656-9661.
36. Li R, Stewart DJ, von Schroeder HP et al (2009) Effect of cell-based VEGF gene therapy on healing of a segmental bone defect. J. Orthop. Res. 27(1): 8-14.
37. Shen X, Wan C, Ramaswamy G, et al., Prolyl hydroxylase inhibitors increase neoangiogenesis and callus formation following femur fracture in mice. J. Orthop. Res. 2009.
38. Street JT, McGrath M, O'Regan K et al (2000) Thromboprophylaxis using a low molecular weight heparin delays fracture repair. Clin. Orthop. Relat. Res. 381: 278-289.
39. Tsopanoglou NE, Andriopoulou P, Maragoudakis ME (2002) On the mechanism of thrombin-induced angiogenesis: involvement of alphavbeta3-integrin. Am. J. Physiol. Cell Physiol. 283(5): C1501-C1510.
40. Mosesson MW (2005) Fibrinogen and fibrin structure and functions. J. Thromb. Haemost. 3(8): 1894-1904.
41. Bar-Shavit R, Eldor A, Vlodavsky I (1989) Binding of thrombin to subendothelial extracellular matrix. Protection and expression of functional properties. J. Clin. Invest. 84(4): 1096-1104.
42. Kon T, Cho TJ, Aizawa T et al (2001) Expression of osteoprotegerin, receptor activator of NF-kappaB ligand (osteoprotegerin ligand) and related proinflammatory cytokines during fracture healing. J Bone Miner. Res. 16(6): 1004-1014.
43. Gerstenfeld LC, Cho TJ, Kon T et al (2003) Impaired fracture healing in the absence of TNF-alpha signaling: the role of TNF-alpha in endochondral cartilage resorption. J. Bone Miner. Res. 18(9): 1584-1592.
44. Gerber HP, Vu TH, Ryan AM et al (1999) VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat. Med. 5(6): 623-628.
45. Carlevaro MF, Cermelli S, Cancedda R et al (2000) Vascular endothelial growth factor (VEGF) in cartilage neovascularization and chondrocyte differentiation: auto-paracrine role during endochondral bone formation. J. Cell Sci. 113(Pt 1): 59-69.
46. Matsumoto T, Cooper GM, Gharaibeh B et al (2009) Cartilage repair in a rat model of osteoarthritis through intraarticular transplantation of muscle-derived stem cells expressing bone morphogenetic protein 4 and soluble Flt-1. Arthritis Rheum. 60(5): 1390-1405.
47. Zelzer E, Mamluk R, Ferrara N et al (2004) VEGFA is necessary for chondrocyte survival during bone development. Development 131(9): 2161-2171.
48. Murata M, Yudoh K, Masuko K (2008) The potential role of vascular endothelial growth factor (VEGF) in cartilage: how the angiogenic factor could be involved in the pathogenesis of osteoarthritis? Osteoarthr. Cartil. 16(3): 279-286.
49. Kloen P, Doty SB, Gordon E et al (2002) Expression and activation of the BMP-signaling components in human fracture nonunions. J. Bone Joint Surg. Am. 84-A(11): 1909-1918.
50. Swiontkowski MF, Aro HT, Donell S et al (2006) Recombinant human bone morphogenetic protein-2 in open tibial fractures. A subgroup analysis of data combined from two prospective randomized studies. J. Bone Joint Surg. Am. 88(6): 1258-1265.
51. Murnaghan M, Li G, Marsh DR (2006) Nonsteroidal anti-inflammatory drug-induced fracture nonunion: an inhibition of angiogenesis? J. Bone Joint Surg. Am. 88(Suppl 3): 140-147.
52. van der Heide HJ, Hannink G, Buma P et al (2008) No effect of ketoprofen and meloxicam on bone graft ingrowth: a bone chamber study in goats. Acta Orthop. 79(4): 548-554.
53. Goodman S, Ma T, Trindade M et al (2002) COX-2 selective NSAID decreases bone ingrowth in vivo. J. Orthop. Res. 20(6): 1164-1169.
54. Simon AM, O'Connor JP (2007) Dose and time-dependent effects of cyclooxygenase-2 inhibition on fracture-healing. J. Bone Joint Surg. Am. 89(3): 500-511.
55. Burd TA, Hughes MS, Anglen JO (2003) Heterotopic ossification prophylaxis with indomethacin increases the risk of long-bone nonunion. J. Bone Joint Surg. Br. 85(5): 700-705.
56. Glassman SD, Rose SM, Dimar JR et al (1998) The effect of postoperative nonsteroidal anti-inflammatory drug administration on spinal fusion. Spine 23(7): 834-838.
57. Hashimoto K, Morishige K, Sawada K et al (2007) Alendronate suppresses tumor angiogenesis by inhibiting Rho activation of endothelial cells. Biochem. Biophys. Res. Commun. 354(2): 478-484.
58. Huang RC, Khan SN, Sandhu HS et al (2005) Alendronate inhibits spine fusion in a rat model. Spine 30(22): 2516-2522.
59. Koedam JA, Smink JJ, van Buul-Offers SC (2002) Glucocorticoids inhibit vascular endothelial growth factor expression in growth plate chondrocytes. Mol. Cell Endocrinol. 197(1-2): 35-44.
60. Sawin PD, Dickman CA, Crawford NR et al (2001) The effects of dexamethasone on bone fusion in an experimental model of posterolateral lumbar spinal arthrodesis. J. Neurosurg. 94(1 Suppl): 76-81.
61. Silcox DH 3rd, Daftari T, Boden SD et al (1995) The effect of nicotine on spinal fusion. Spine 20(14): 1549-1553.
62. Grey A (2008) Skeletal consequences of thiazolidinedione therapy. Osteoporos. Int. 19(2): 129-137.
63. Aspenberg P (2005) Drugs and fracture repair. Acta Orthop. 76(6): 741-748.
64. Bartlett CS 3rd, Weiner LS, Yang EC (1997) Treatment of type II and type III open tibia fractures in children. J. Orthop. Trauma 11(5): 357-362.
65. Utvag SE, Grundnes O, Reikeraos O (1996) Effects of periosteal stripping on healing of segmental fractures in rats. J. Orthop. Trauma 10(4): 279-284.
66. Dirschl DR, Duff GP, Dahners LE et al (1998) High pressure pulsatile lavage irrigation of intraarticular fractures: effects on fracture healing. J. Orthop. Trauma 12(7): 460-463.