Document Type

Journal Article

Department/Unit

School of Chinese Medicine

Language

English

Abstract

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.

Publication Date

3-2015

Source Publication Title

Scientific Reports

Volume

5

Start Page

8856

Publisher

Nature Publishing Group

Peer Reviewed

1

Copyright

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material.

Funder

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).

DOI

10.1038/srep08856

Link to Publisher's Edition

http://dx.doi.org/10.1038/srep08856

ISSN (print)

20452322

ISSN (electronic)

20452322

Additional Files

JA-4984-27418_suppl.doc (322 kB)

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