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Src inhibitor reduces permeability without disturbing vascularization and prevents bone destruction in steroid-associated osteonecrotic lesions in rabbits.

He YX, Liu J, Guo B, Wang YX, Pan X, Li D, Tang T, Chen Y, Peng S, Bian Z, Liang Z, Zhang BT, Lu A, Zhang G - Sci Rep (2015)

Bottom Line: The incidence of the destructive repair in the Anti-VEGF Group, Src-Inhibition Group and Supplement &Inhibition Group was all significantly lower than that in the Control Group.The trabecular structure was improved in Src-Inhibition Group and Supplement &Inhibition Group.Src inhibitor could reduce permeability without disturbing vascularization and prevent destructive repair in steroid-associated osteonecrosis.

View Article: PubMed Central - PubMed

Affiliation: 1] Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China [2] Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong SAR, China [3] Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University, Hong Kong SAR, China [4] Institute of Integrated Bioinformedicine &Translational Science, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, China [5] Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone &Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu, China [6] Hong Kong Baptist University - Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen, China.

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 &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 &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 &Inhibition Group, while the hyperpermeability was inhibited in Anti-VEGF Group, Src-Inhibition Group and Supplement &Inhibition Group. The trabecular structure was improved in Src-Inhibition Group and Supplement &Inhibition Group. Src inhibitor could reduce permeability without disturbing vascularization and prevent destructive repair in steroid-associated osteonecrosis.

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Angiographic analyses of the size and thickness of the vessel structures in the bilateral proximal femora of rabbits.(A). Representative 3-D angiogram at 4 weeks post-administration in different groups. (B) Size distribution of angiographic structure 4 weeks post-administration in different groups. N = 8
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f4: Angiographic analyses of the size and thickness of the vessel structures in the bilateral proximal femora of rabbits.(A). Representative 3-D angiogram at 4 weeks post-administration in different groups. (B) Size distribution of angiographic structure 4 weeks post-administration in different groups. N = 8

Mentions: Figure 4 presents representative 3-D angiograms and histograms depicting the size of angiographic structures. The Control Group showed large-sized (400 ~ 600 μm) vessel-like structures (VLS) surrounded by both fewer small-sized (36 ~ 200 μm) VLS and many medium-sized (200 ~ 400 μm) disseminated leakage particle–like structures (DLPLS); The Anti-VEGF Group showed only dilated and large-sized VLS, but neither small-sized VLS nor medium-sized DLPLS; The Src-Inhibition Group showed some dilated and large-sized VLS surrounded by more small-sized VLS but no medium-sized DLPLS compared to Control Group; In the VEGF-Supplement Group, although there are more small-sized VLS, but there are also more medium-sized DLPLS compared to the control; In the Supplement & Inhibition Group, there are more small-sized VLS with nearly no medium-sized DLPLS compared to Control Group (Figure 4A).


Src inhibitor reduces permeability without disturbing vascularization and prevents bone destruction in steroid-associated osteonecrotic lesions in rabbits.

He YX, Liu J, Guo B, Wang YX, Pan X, Li D, Tang T, Chen Y, Peng S, Bian Z, Liang Z, Zhang BT, Lu A, Zhang G - Sci Rep (2015)

Angiographic analyses of the size and thickness of the vessel structures in the bilateral proximal femora of rabbits.(A). Representative 3-D angiogram at 4 weeks post-administration in different groups. (B) Size distribution of angiographic structure 4 weeks post-administration in different groups. N = 8
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4352921&req=5

f4: Angiographic analyses of the size and thickness of the vessel structures in the bilateral proximal femora of rabbits.(A). Representative 3-D angiogram at 4 weeks post-administration in different groups. (B) Size distribution of angiographic structure 4 weeks post-administration in different groups. N = 8
Mentions: Figure 4 presents representative 3-D angiograms and histograms depicting the size of angiographic structures. The Control Group showed large-sized (400 ~ 600 μm) vessel-like structures (VLS) surrounded by both fewer small-sized (36 ~ 200 μm) VLS and many medium-sized (200 ~ 400 μm) disseminated leakage particle–like structures (DLPLS); The Anti-VEGF Group showed only dilated and large-sized VLS, but neither small-sized VLS nor medium-sized DLPLS; The Src-Inhibition Group showed some dilated and large-sized VLS surrounded by more small-sized VLS but no medium-sized DLPLS compared to Control Group; In the VEGF-Supplement Group, although there are more small-sized VLS, but there are also more medium-sized DLPLS compared to the control; In the Supplement & Inhibition Group, there are more small-sized VLS with nearly no medium-sized DLPLS compared to Control Group (Figure 4A).

Bottom Line: The incidence of the destructive repair in the Anti-VEGF Group, Src-Inhibition Group and Supplement &Inhibition Group was all significantly lower than that in the Control Group.The trabecular structure was improved in Src-Inhibition Group and Supplement &Inhibition Group.Src inhibitor could reduce permeability without disturbing vascularization and prevent destructive repair in steroid-associated osteonecrosis.

View Article: PubMed Central - PubMed

Affiliation: 1] Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China [2] Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong SAR, China [3] Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University, Hong Kong SAR, China [4] Institute of Integrated Bioinformedicine &Translational Science, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, China [5] Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone &Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu, China [6] Hong Kong Baptist University - Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen, China.

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 &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 &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 &Inhibition Group, while the hyperpermeability was inhibited in Anti-VEGF Group, Src-Inhibition Group and Supplement &Inhibition Group. The trabecular structure was improved in Src-Inhibition Group and Supplement &Inhibition Group. Src inhibitor could reduce permeability without disturbing vascularization and prevent destructive repair in steroid-associated osteonecrosis.

Show MeSH
Related in: MedlinePlus