School of Chinese Medicine
To examine the therapeutic effect of Src inhibitor on the VEGF mediating vascular hyperpermeability and bone destruction within steroid-associated osteonecrotic lesions in rabbits. Rabbits with high risk for progress to destructive repair in steroid-associated osteonecrosis were selected according to our published protocol. The selected rabbits were systemically administrated with either Anti-VEGF antibody (Anti-VEGF Group) or Src inhibitor (Src-Inhibition Group) or VEGF (VEGF-Supplement Group) or a combination of VEGF and Src inhibitor (Supplement and Inhibition Group) or control vehicle (Control Group) for 4 weeks. At 0, 2 and 4 weeks after administration, in vivo dynamic MRI, micro-CT based-angiography, histomorphometry and immunoblotting were employed to evaluate the vascular and skeletal events in different groups. The incidence of the destructive repair in the Anti-VEGF Group, Src-Inhibition Group and Supplement and Inhibition Group was all significantly lower than that in the Control Group. The angiogenesis was promoted in VEGF-Supplement Group, Src-Inhibition Group and Supplement and Inhibition Group, while the hyperpermeability was inhibited in Anti-VEGF Group, Src-Inhibition Group and Supplement and Inhibition Group. The trabecular structure was improved in Src-Inhibition Group and Supplement and Inhibition Group. Src inhibitor could reduce permeability without disturbing vascularization and prevent destructive repair in steroid-associated osteonecrosis.
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Nature Publishing Group
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This work was supported by the Hong Kong General Research Fund (12102914 and HKBU 478312), Interdisciplinary Research Matching Scheme (IRMS) of Hong Kong Baptist University (RC-IRMS/13-14/02 and RC-IRMS/13-14/03), the Science and Technology Innovation Commission of Shenzhen Municipality (SCM-2013-SZTIC-001), Natural Science Foundation Council (81272045 and 81401833).
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He, Y., Liu, J., Guo, B., Wang, Y., Pan, X., Li, D., Tang, T., Chen, Y., Peng, S., Bian, Z., Liang, Z., Zhang, B., Lu, A., & Zhang, G. (2015). Src inhibitor reduces permeability without disturbing vascularization and prevents bone destruction in steroid-associated osteonecrotic lesions in rabbits. Scientific Reports, 5, 8856. https://doi.org/10.1038/srep08856