Blockage of Src by Specific siRNA as a Novel Therapeutic Strategy to Prevent Destructive Repair in Steroid‐Associated Osteonecrosis in Rabbits

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 wa...
Source: Journal of Bone and Mineral Research - Category: Orthopaedics Authors: Tags: Original Article Source Type: research