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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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Related in: MedlinePlus

Shift of the trabecular structural profile during osteonecrotic lesion repair in different groups.(A). Size distribution of trabecular bone of osteonecrotic lesion at 4-weeks post-administration in different groups. (B). Representative 3-D structure of trabecular bone of osteonecrotic lesion at 4-weeks post-administration in different groups. N = 7
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f2: Shift of the trabecular structural profile during osteonecrotic lesion repair in different groups.(A). Size distribution of trabecular bone of osteonecrotic lesion at 4-weeks post-administration in different groups. (B). Representative 3-D structure of trabecular bone of osteonecrotic lesion at 4-weeks post-administration in different groups. N = 7

Mentions: For trabecular structure of osteonecrotic lesions by micro-CT measurement, there is no difference in quantities of either small-sized (0.036 ~ 0.2 mm) or large-sized (0.2 ~ 0.4 mm) trabecular bone between Anti-VEGF Group and Baseline Group. Compared to that at Baseline, less large-sized and more small-sized trabecular bones were found in Control Group and VEGF-Supplement Group, whereas more large-sized and less small-sized trabecular bone were found in Src-Inhibition Group and Supplement & Inhibition Group. Apparently, the size distribution of the trabeculae shifted toward thinning in the Control Group when compared to the baseline, and it further shifted toward thinning in the VEGF-Supplement Group when compared to the Control Group, whereas it hardly shifted in the Anti-VEGF Group or shifted toward moderately thickening in Src-Inhibition Group and Supplement & Inhibition Group when compared to the baseline. (Figure 2)


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)

Shift of the trabecular structural profile during osteonecrotic lesion repair in different groups.(A). Size distribution of trabecular bone of osteonecrotic lesion at 4-weeks post-administration in different groups. (B). Representative 3-D structure of trabecular bone of osteonecrotic lesion at 4-weeks post-administration in different groups. N = 7
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Shift of the trabecular structural profile during osteonecrotic lesion repair in different groups.(A). Size distribution of trabecular bone of osteonecrotic lesion at 4-weeks post-administration in different groups. (B). Representative 3-D structure of trabecular bone of osteonecrotic lesion at 4-weeks post-administration in different groups. N = 7
Mentions: For trabecular structure of osteonecrotic lesions by micro-CT measurement, there is no difference in quantities of either small-sized (0.036 ~ 0.2 mm) or large-sized (0.2 ~ 0.4 mm) trabecular bone between Anti-VEGF Group and Baseline Group. Compared to that at Baseline, less large-sized and more small-sized trabecular bones were found in Control Group and VEGF-Supplement Group, whereas more large-sized and less small-sized trabecular bone were found in Src-Inhibition Group and Supplement & Inhibition Group. Apparently, the size distribution of the trabeculae shifted toward thinning in the Control Group when compared to the baseline, and it further shifted toward thinning in the VEGF-Supplement Group when compared to the Control Group, whereas it hardly shifted in the Anti-VEGF Group or shifted toward moderately thickening in Src-Inhibition Group and Supplement & Inhibition Group when compared to the baseline. (Figure 2)

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