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

Rumney, Robin M. H.; Lanham, Stuart A.; Kanczler, Janos M.; Kao, Alexander P.; Thiagarajan, Lalitha; Dixon, James E.; Tozzi, Gianluca; Oreffo, Richard O. C.

Abstract

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 efcacy 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 quantifable 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 efects by promoting VEGF protein secretion from MG-63VEGF165 cells in vitro, which resulted in signifcantly 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.

Citation

Rumney, R. M. H., Lanham, S. A., Kanczler, J. M., Kao, A. P., Thiagarajan, L., Dixon, J. E., …Oreffo, R. O. C. (2019). In vivo delivery of VEGF RNA and protein to increase osteogenesis and intraosseous angiogenesis. Scientific Reports, 9(1), Article 17745. https://doi.org/10.1038/s41598-019-53249-4

• Journal Article Type: Article
• Acceptance Date: Oct 22, 2019
• Online Publication Date: Nov 28, 2019
• Publication Date: 2019-12
• Deposit Date: Jan 10, 2020
• Publicly Available Date: Jan 10, 2020
• Journal: Scientific Reports
• Print ISSN: 2045-2322
• Electronic ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 1
• Article Number: 17745
• DOI: https://doi.org/10.1038/s41598-019-53249-4
• Public URL: https://nottingham-repository.worktribe.com/output/3479103
• Publisher URL: https://www.nature.com/articles/s41598-019-53249-4