In vivo endochondral bone formation using a bone morphogenetic protein 2 adenoviral vector.

In vivo endochondral bone formation using a bone morphogenetic protein 2 adenoviral vector. Research Abstract Details 

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In vivo endochondral bone formation using a bone morphogenetic protein 2 adenoviral vector. Abstract Text:

T D Alden,D D Pittman,G R Hankins,E J Beres,J A Engh,S Das,S B Hudson,K M Kerns,D F Kallmes,G A Helm,

Bone morphogenetic proteins (BMPs) are polypeptides that induce ectopic bone formation in standard rat in vivo assay systems. Previous studies have demonstrated the clinical utility of these proteins in spinal fusion, fracture healing, and prosthetic joint stabilization. Gene therapy is also a theoretically attractive technique to express BMPs clinically, since long-term, regulatable gene expression and systemic delivery with tissue-specific expression may be possible in future. This study was performed to determine whether an adenoviral vector containing the BMP-2 gene can be used to express BMP-2 in vitro and promote endochondral bone formation in vivo. In vitro, U87 MG cells transduced per cell with 20 MOI of an adenoviral construct containing the BMP-2 gene under the control of the universal CMV promoter (Ad-BMP-2) showed positive antibody staining for the BMP-2 protein at posttransfection day 2. The synthesis and secretion of active BMP-2 into the conditioned medium of Ad-BMP-2-transduced 293 cells were confirmed by Western blot analysis and the induction of alkaline phosphatase activity in a W-20 stromal cell assay. In vivo, Sprague-Dawley rats and athymic nude rats were injected with Ad-BMP-2 in the thigh musculature and were sacrificed on day 3, 6, 9, 12, 16, 21, 60, and 110 for histological analysis. The Sprague-Dawley rats showed evidence of acute inflammation, without ectopic bone formation, at the injection sites. In the athymic nude rats, BMP-2 gene therapy induced mesenchymal stem cell chemotaxis and proliferation, with subsequent differentiation to chondrocytes. The chondrocytes secreted a cartilaginous matrix, which then mineralized and was replaced by mature bone. This study demonstrates that a BMP-2 adenoviral vector can be utilized to produce BMP-2 by striated muscle cells in athymic nude rats, leading to endochondral bone formation. However, in immunocompetent animals the endochondral response is attenuated, secondary to the massive immune response elicited by the first-generation adenoviral construct.

In vivo endochondral bone formation using a bone morphogenetic protein 2 adenoviral vector. Publishing Authors By Initials

TD Alden,DD Pittman,GR Hankins,EJ Beres,JA Engh,S Das,SB Hudson,KM Kerns,DF Kallmes,GA Helm,

For similar peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research

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In vivo endochondral bone formation using a bone morphogenetic protein 2 adenoviral vector. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Human gene therapy

VOLUME: 10

Page Numbers: 2245-53

Journal Abbreviation: Hum. Gene Ther.

ISSN: 1043-0342

DAY: 1

MONTH: Sep

YEAR: 1999

In vivo endochondral bone formation using a bone morphogenetic protein 2 adenoviral vector. Information

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LANGUAGE: eng

NlmUniqueID: 9008950

In vivo endochondral bone formation using a bone morphogenetic protein 2 adenoviral vector. Keywords Mesh Terms:

KEYWORDS: Transforming Growth Factor beta

MESH TERMS: radiography

Chemical & Substance for Abstract: In vivo endochondral bone formation using a bone morphogenetic protein 2 adenoviral vector. Information

Substance Name: bone morphogenetic protein 2

Registry Number: 0

Grant and Affiliation Information for In vivo endochondral bone formation using a bone morphogenetic protein 2 adenoviral vector.

AFFILIATION: Department of Neurosurgery, University of Virginia, Charlottesville 22908, USA.

Country: UNITED STATES

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MEDLINETA: Hum Gene Ther

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