Blockage of Src by Specific siRNA as a Novel Therapeutic Strategy to Prevent Destructive Repair in Steroid-Associated Osteonecrosis in Rabbits
文献类型：期刊论文
| 作者 | Li-zhen Zheng; Hui-juan Cao; Shi-hui Chen; Tao Tang; ,Wei-min Fu; ,Le Huang; Dick Ho Kiu Chow; Yi-xiang Wang; James Francis Griffith; Wei He |
| 刊名 | JOURNAL OF BONE AND MINERAL RESEARCH
 |
| 出版日期 | 2015 |
| 英文摘要 | Vascular hyperpermeability and highly upregulated bone resorption in the destructive repair progress of steroid-associated osteonecrosis (SAON) are associated with a high expression of VEGF and high Src activity (Src is encoded by the cellular sarcoma [c-src] gene). This study was designed to prove our hypothesis that blocking the VEGF-Src signaling pathway by specific Src siRNA is able to prevent destructive repair in a SAON rabbit model. Destructive repair in SAON was induced in rabbits. At 2, 4, and 6 weeks after SAON induction, VEGF, anti-VEGF, Src siRNA, Src siRNA+VEGF, control siRNA, and saline were introduced via intramedullary injection into proximal femora for each group, respectively. Vascularization and permeability were quantified by dynamic contrast-enhanced (DCE) MRI. At week 6 after SAON induction, proximal femurs were dissected for micro-computed tomography (CT)-based trabecular architecture with finite element analysis (FEA), CT-based angiography, and histological analysis. Histological evaluation revealed that VEGF enhanced destructive repair, whereas anti-VEGF prevented destructive repair and Src siRNA and Src siRNA+VEGF prevented destructive repair and enhanced reparative osteogenesis. Findings of angiography and histomorphometry were consistent with those determined by DCE MRI. Src siRNA inhibited VEGF-mediated vascular hyperpermeability but preserved VEGF-induced neovascularization. Bone resorption was enhanced in the VEGF group and inhibited in the anti-VEGF, Src siRNA, Src siRNA+VEGF groups as determined by both 3D CT and 2D histomorphometry. FEA showed higher estimated failure load in the Src siRNA and Src siRNA+VEGF groups when compared to the vehicle control group. Blockage of VEGF-Src signaling pathway by specific Src siRNA was able to prevent steroid-associated destructive repair while improving reconstructive repair in SAON, which might become a novel therapeutic strategy. (c) 2015 American Society for Bone and Mineral Research. |
| 收录类别 | SCI |
| 原文出处 | http://onlinelibrary.wiley.com/doi/10.1002/jbmr.2542/abstract |
| 语种 | 英语 |
| 源URL | [http://ir.siat.ac.cn:8080/handle/172644/7198]  |
| 专题 | 深圳先进技术研究院_医工所 |
| 作者单位 | JOURNAL OF BONE AND MINERAL RESEARCH |
| 推荐引用方式 GB/T 7714 | Li-zhen Zheng,Hui-juan Cao,Shi-hui Chen,et al. Blockage of Src by Specific siRNA as a Novel Therapeutic Strategy to Prevent Destructive Repair in Steroid-Associated Osteonecrosis in Rabbits[J]. JOURNAL OF BONE AND MINERAL RESEARCH,2015. |
| APA | Li-zhen Zheng.,Hui-juan Cao.,Shi-hui Chen.,Tao Tang.,,Wei-min Fu.,...&Ling Qin.(2015).Blockage of Src by Specific siRNA as a Novel Therapeutic Strategy to Prevent Destructive Repair in Steroid-Associated Osteonecrosis in Rabbits.JOURNAL OF BONE AND MINERAL RESEARCH. |
| MLA | Li-zhen Zheng,et al."Blockage of Src by Specific siRNA as a Novel Therapeutic Strategy to Prevent Destructive Repair in Steroid-Associated Osteonecrosis in Rabbits".JOURNAL OF BONE AND MINERAL RESEARCH (2015). |
入库方式： OAI收割
来源：深圳先进技术研究院
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