体内递送VEGF RNA和蛋白质以增加成骨和骨内血管生成。,Scientific Reports

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体内递送VEGF RNA和蛋白质以增加成骨和骨内血管生成。
Scientific Reports ( IF 3.8 ) Pub Date : 2019-11-28 , DOI: 10.1038/s41598-019-53249-4
Robin M H Rumney _{1,

2} , Stuart A Lanham ₁ , Janos M Kanczler ₁ , Alexander P Kao ₃ , Lalitha Thiagarajan ₄ , James E Dixon ₄ , Gianluca Tozzi ₃ , Richard O C Oreffo ₁

Affiliation

从发展中的骨骼异常到受损的骨修复，病理状态下的骨脉管系统不足是关键因素。血管化取决于血管内皮生长因子（VEGF），该因子可驱动血管生成和成骨。这项研究的目的是检查在体外和体内模型系统中用VEGF RNA转染或重组人VEGF165蛋白（rhVEGF165）的递送后血管和骨形成的功效。为了量化骨骼内的血管，使用高分辨率X射线计算机断层扫描（XCT）开发了一种创新方法来生成可量化的三维重建物。应用rhVEGF165增强成骨作用，体外给药后人成骨样MG-63细胞增殖增加以及颅骨厚度增加所证明。相反，用VEGF RNA转染通过促进体外MG-63VEGF165细胞的VEGF蛋白分泌来触发血管生成作用，从而在卵内绒毛膜尿囊（CAM）分析中导致血管生成显着增加。此外，在体内用VEGF RNA直接转染骨骼会增加骨内血管分支。这项研究表明，与单一高剂量的VEGF相比，持续供应对血管生成和成骨的重要性，并说明了XCT在描绘3D，骨骼中的血管连通性方面的潜力。VEGF RNA的转染通过促进体外MG-63VEGF165细胞的VEGF蛋白分泌来触发血管生成作用，从而在卵内绒毛膜尿囊（CAM）分析中显着增加了血管生成。此外，在体内用VEGF RNA直接转染骨骼会增加骨内血管分支。这项研究证明了与单一高剂量的VEGF相比，持续供应对血管生成和成骨的重要性，并说明了XCT在描绘3D，骨骼中的血管连通性方面的潜力。VEGF RNA的转染通过促进体外MG-63VEGF165细胞的VEGF蛋白分泌来触发血管生成作用，从而在卵内绒毛膜尿囊（CAM）分析中显着增加了血管生成。此外，在体内用VEGF RNA直接转染骨骼会增加骨内血管分支。这项研究表明，与单一高剂量的VEGF相比，持续供应对血管生成和成骨的重要性，并说明了XCT在描绘3D，骨骼中的血管连通性方面的潜力。

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In vivo delivery of VEGF RNA and protein to increase osteogenesis and intraosseous angiogenesis.

Deficient bone vasculature is a key component in pathological conditions ranging from developmental skeletal abnormalities to impaired bone repair. Vascularisation is dependent upon vascular endothelial growth factor (VEGF), which drives both angiogenesis and osteogenesis. The aim of this study was to examine the efficacy of blood vessel and bone formation following transfection with VEGF RNA or delivery of recombinant human VEGF165 protein (rhVEGF165) across in vitro and in vivo model systems. To quantify blood vessels within bone, an innovative approach was developed using high-resolution X-ray computed tomography (XCT) to generate quantifiable three-dimensional reconstructions. Application of rhVEGF165 enhanced osteogenesis, as evidenced by increased human osteoblast-like MG-63 cell proliferation in vitro and calvarial bone thickness following in vivo administration. In contrast, transfection with VEGF RNA triggered angiogenic effects by promoting VEGF protein secretion from MG-63VEGF165 cells in vitro, which resulted in significantly increased angiogenesis in the chorioallantoic (CAM) assay in ovo. Furthermore, direct transfection of bone with VEGF RNA in vivo increased intraosseous vascular branching. This study demonstrates the importance of continuous supply as opposed to a single high dose of VEGF on angiogenesis and osteogenesis and, illustrates the potential of XCT in delineating in 3D, blood vessel connectivity in bone.

更新日期：2019-11-29

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