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

In vivo delivery of VEGF RNA and protein to increase osteogenesis and intraosseous angiogenesis
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.
2045-2322
1-10
Rumney, Robin
fa3de9f8-b604-44e2-9e72-3e57980ce67f
Lanham, Stuart
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Kanczler, Janos
eb8db9ff-a038-475f-9030-48eef2b0559c
Kao, Alexander
a07dea90-fcb7-47c0-9637-ce8e5e2a678b
Thiagarajan, Lalitha
f6b38884-dfc6-447d-9746-5223ccd9f03d
Dixon, James
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Tozzi, Gianluca
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Oreffo, Richard
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Rumney, Robin
fa3de9f8-b604-44e2-9e72-3e57980ce67f
Lanham, Stuart
28fdbbef-e3b6-4fdf-bd0f-4968eeb614d6
Kanczler, Janos
eb8db9ff-a038-475f-9030-48eef2b0559c
Kao, Alexander
a07dea90-fcb7-47c0-9637-ce8e5e2a678b
Thiagarajan, Lalitha
f6b38884-dfc6-447d-9746-5223ccd9f03d
Dixon, James
0ec5d360-2282-485c-962d-4c272a6b9a93
Tozzi, Gianluca
d9d96325-6d17-4b76-8e45-05727e45c694
Oreffo, Richard
ff9fff72-6855-4d0f-bfb2-311d0e8f3778

Rumney, Robin, Lanham, Stuart, Kanczler, Janos, Kao, Alexander, Thiagarajan, Lalitha, Dixon, James, Tozzi, Gianluca and Oreffo, Richard (2019) In vivo delivery of VEGF RNA and protein to increase osteogenesis and intraosseous angiogenesis. Scientific Reports, 9, 1-10, [17745]. (doi:10.1038/s41598-019-53249-4).

Record type: Article

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 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.

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More information

Accepted/In Press date: 22 October 2019
e-pub ahead of print date: 28 November 2019
Published date: 28 November 2019

Identifiers

Local EPrints ID: 436002
URI: http://eprints.soton.ac.uk/id/eprint/436002
ISSN: 2045-2322
PURE UUID: b6446004-4b8a-4d56-bde2-6c13553d33a3
ORCID for Stuart Lanham: ORCID iD orcid.org/0000-0002-4516-264X
ORCID for Janos Kanczler: ORCID iD orcid.org/0000-0001-7249-0414
ORCID for Richard Oreffo: ORCID iD orcid.org/0000-0001-5995-6726

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Date deposited: 26 Nov 2019 17:30
Last modified: 07 Oct 2020 01:51

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