BLOCKAGE OF SRC BY SPECIFIC SIRNA AS A NOVEL THERAPEUTIC STRATEGY TO PREVENTDESTRUCTIVE REPAIR IN STEROID-ASSOCIATED OSTEONECROSIS

	BLOCKAGE OF SRC BY SPECIFIC SIRNA AS A NOVEL THERAPEUTIC STRATEGY TO PREVENTDESTRUCTIVE REPAIR IN STEROID-ASSOCIATED OSTEONECROSIS
	Zheng L.; Cao H. -J.; Fu W. -M.; Wang X. -L.; Chen S. -H.; Huang L.; Tian L.; Wang J. -L.; Qin L.
刊名	OSTEOPOROSIS INTERNATIONAL
	2013
英文摘要	Vascular hyperpermeability and highly up-regulated bone resorption in the destructive repair progress of steroid-associated osteonecrosis (SAON) are associated with a high expression of VEGF and high Src activity. This study was designed to prove our hypothesis that blocking VEGF-Src signaling pathway by specific Src siRNA was able to prevent destructive repair in a SAON rabbit model. Destructive repair in SAON was induced in rabbits. At 2, 4, 6 weeks after SAON induction, VEGF, anti-VEGF, Src siRNA, Src siRNA + VEGF, control siRNA and saline were intramedullary injected 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 femora were dissected for micro-CT-based trabecular architecture with finite element analysis (FEA), micro-CT-based angiography, and histological analysis. Histological evaluation revealed that VEGF enhanced destructive repair while anti-VEGF prevented destructive repair, siSrc and siSrc + 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, siSrc, siSrc + VEGF groups as determined by both 3D microCT and 2D histomorphometry. FEA showed higher estimated failure load in the siSrc and siSrc + 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. This article is protected by copyright. All rights reserved
收录类别	SCI
原文出处	http://onlinelibrary.wiley.com/doi/10.1002/jbmr.2542/abstract
语种	英语
内容类型	期刊论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/4911]
专题	深圳先进技术研究院_医工所
作者单位	OSTEOPOROSIS INTERNATIONAL
推荐引用方式 GB/T 7714	Zheng L.,Cao H. -J.,Fu W. -M.,et al. BLOCKAGE OF SRC BY SPECIFIC SIRNA AS A NOVEL THERAPEUTIC STRATEGY TO PREVENTDESTRUCTIVE REPAIR IN STEROID-ASSOCIATED OSTEONECROSIS[J]. OSTEOPOROSIS INTERNATIONAL,2013.
APA	Zheng L..,Cao H. -J..,Fu W. -M..,Wang X. -L..,Chen S. -H..,...&Qin L..(2013).BLOCKAGE OF SRC BY SPECIFIC SIRNA AS A NOVEL THERAPEUTIC STRATEGY TO PREVENTDESTRUCTIVE REPAIR IN STEROID-ASSOCIATED OSTEONECROSIS.OSTEOPOROSIS INTERNATIONAL.
MLA	Zheng L.,et al."BLOCKAGE OF SRC BY SPECIFIC SIRNA AS A NOVEL THERAPEUTIC STRATEGY TO PREVENTDESTRUCTIVE REPAIR IN STEROID-ASSOCIATED OSTEONECROSIS".OSTEOPOROSIS INTERNATIONAL (2013).