Traditional methods to establish animal model of osteonecrosis of the femoral head (ONFH) are not satisfactory because of the undefined underlying mechanism, low rate of the disease, and high incidence of mortality. The present study was to induce ONFH in a rat model through periarticular injection of vascular endothelial growth factor (VEGF) receptor 2 antibody.
Materials and methods
Eighty Sprague–Dawley rats were divided into four groups randomly and equally. VEGF receptor 2 antibody solution with a concentration of 50 μg/mL (group A), 25 μg/mL (group B), and 12.5 μg/mL (group C) was injected periarticularly to the capsular attachment to proximal femur, respectively. The injection lasted 4 continuous days, with a total volume of 2 mL. The rats in the fourth group were treated by saline for control (group D). Two weeks after the first injection, histologic and micro-computed tomographic examinations were used to investigate the presence of ONFH.
Histologically, there were 90% of rats that developed ONFH in group A, 60% in group B, and 20% in group C, whereas no ONFH was found in group D. The density of intraosseous vessels was suppressed significantly by the antibody. Radiologically, the features of ONFH including deformation of the femoral head were revealed. There was no occurrence of lethal complications.
VEGF receptor 2 antibody can induce ONFH in the rat with a high incidence of the disease. Local blockage of angiogenesis can be used as an effective method to establish animal model of ONFH.
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- Expression of the angiomatrix and angiogenic proteins CYR61, CTGF, and VEGF in osteonecrosis of the femoral head.J Orthop Res. 2006; 24: 945
- VEGF/VEGFR pathway inhibitors as anti-angiogenic agents: present and future.Curr Cancer Drug Targets. 2011; 11: 624
- Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity.J Clin Invest. 2000; 105: R15
- Inhibition of tumor angiogenesis by antibodies, synthetic small molecular and natural products.Curr Med Chem. 2011; 18: 3136
- Sustained vascular endothelial growth factor blockade by antivascular endothelial growth factor antibodies results in nonunion in the process of fracture healing in rabbits.J Trauma. 2009; 66: 1180
- Vascular endothelial growth factor (VEGF) gene transfer enhances surgical revascularization of necrotic bone.J Orthop Res. 2005; 23: 469
- VEGF-promoted surgical angiogenesis in necrotic bone.Microsurgery. 2004; 24: 85
- Osteogenesis induced by extracorporeal shockwave in treatment of delayed osteotendinous junction healing.J Orthop Res. 2010; 28: 70
- Experimental avascular osteonecrosis.Curr Orthop. 2001; 15: 57
- Osteonecrosis development in a novel rat model characterized by a single application of oxidative stress.Arthritis Rheumatism. 2011; 63: 2138
- Osteonecrosis induced by a single administration of low-dose lipopolysaccharide in rabbits.Bone. 2001; 28: 641
- A new animal model of femoral head necrosis induced by intraosseous injection of ethanol.Lab Animals. 2002; 36: 173
- A new animal model of femoral head osteonecrosis: one that progresses to human-like mechanical failure.J Orthop Res. 2002; 20: 303
- Experimental osteonecrosis induced by a combination of low-dose methylprednisolone in rabbits.Joint Bone Spine. 2008; 75: 573
- Vasculature deprivation—induced osteonecrosis of the rat femoral head as a model for therapeutic trials.Theoretical Biology and Medical Modelling. 2005; 2: 24
- Femoral head deformation and repair following induction ischemic necrosis. A histologic and magnetic resonance imaging study in the piglet.J Bone Joint Surg Am. 2009; 91: 2903
- The pathogenesis and prevention of steroid induced osteonecrosis.Clin Orthop Relat Res. 2000; 370: 295
- Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoid. Potential mechanisms of their deleterious effects on bone.J Clin Invest. 1998; 102: 274
- Femoral head osteonecrosis can be caused by disruption of the systemic immune response via the toll-like receptor 4 signalling pathway.Rheumatology. 2009; 48: 227
- Femoral head blood flow reduction and hypercoagulability under 24 h megadose steroid treatment in pigs.J Orthop Res. 2004; 22: 501
- A rat model of early stage osteonecrosis induced by glucocorticoid.J Orthop Surg Res. 2011; 6: 62
- A mouse model for glucocorticoid-induced osteonecrosis: effect of a steroid holiday.J Orthop Res. 2009; 27: 169
- Effects of pulse methylprednisolone on bone and marrow tissue. Corticosteroid-induced osteonecrosis in rabbits.Arthritis Rheumatism. 1997; 40: 2055
- Angiogenesis and bone repair.DTT. 2003; 8: 980
- Sustained delivery of vascular endothelial growth factor with alginate beads.J Control Release. 2004; 96: 463
Published online: February 13, 2013
Accepted: January 22, 2013
Received in revised form: January 21, 2013
Received: November 18, 2012
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