Research article summary (published 4 Jun 2000):

Gene therapy for bone formation: in vitro and in vivo osteogenic activity of an adenovirus expressing BMP7.

Full Abstract

Bone morphogenetic proteins (BMPs) are well-established agents for inducing orthotopic and ectopic bone formation. However, their clinical usefulness as regenerative agents may be limited by a short in vivo half-life and low specific activity. BMP gene therapy is an alternative route for exploiting the bone-inductive activity of this class of molecules. To test the feasibility of this approach, we examined the osteogenic activity of AdCMV-BMP7, an adenovirus containing BMP7 cDNA under control of the CMV promoter that was constructed using Cre/lox recombination (Hardy et al. [1997] J. Virol. 71:1842-1849). Adenovirus vectors were shown to readily infect a wide variety of cell types in vitro including osteoblasts, fibroblasts, and myoblasts. COS7 cells transduced with AdCMV-BMP7 produced high levels of BMP-7 (approximately 0.5 microg/10(6) cells). Furthermore, transduction of C2C12 murine myoblast cells with AdCMVBMP-7 suppressed the muscle phenotype and induced in vitro osteoblast differentiation. To test its in vivo biological activity, AdCMV-BMP7 was mixed with a bovine bone-derived collagen carrier (10(8) plaque-forming units virus/site) and was implanted into mouse muscle and dermal pouches. In both cases, an ossicle containing cortical and trabecular bone and a clearly defined marrow cavity formed at the site of virus implantation within 4 weeks. These data demonstrate that AdCMV-BMP7 transduced cells produce biologically active BMP-7 both in vitro and in vivo and show that gene therapy by direct viral transduction using a virus/matrix implant may be a viable route for stimulating bone regeneration. Copyright 2000 Wiley-Liss, Inc.

Author information

Author/s: Franceschi, R T (RT); Wang, D (D); Krebsbach, P H (PH); Rutherford, R B (RB);

Affiliation: Departments of Periodontics/Prevention/Geriatrics, School of Dentistry, University of Michigan, Ann Arbor 48109-1078, USA. rennyf(-atsign-)umich.edu

Grants: DE11732 (Agency:NIDCR NIH HHS) ; DE12211 (Agency:NIDCR NIH HHS) ; DE12466 (Agency:NIDCR NIH HHS)

Journal and publication information

Publication Type: In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.

Journal: Journal of cellular biochemistry (J Cell Biochem), published in UNITED STATES. (Language: eng)

Reference: 2000-Jun; vol 78 (issue 3) : pp 476-86

Dates: Created 2000/08/24; Completed 2000/08/24; Revised 2008/11/21;

PMID: 10861845, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adenoviridae - genetics; metabolism Animals Blotting, Western Bone Development Bone Morphogenetic Protein 7 Bone Morphogenetic Proteins - biosynthesis; genetics Bone and Bones - cytology; metabolism; virology COS Cells - metabolism; virology Cattle Cells, Cultured Fibroblasts - cytology; metabolism; virology Gene Expression

Gene Expression Gene Therapy Genetic Vectors Humans Mice Muscle, Skeletal - cytology; metabolism; virology Osteoblasts - cytology; metabolism; virology Osteogenesis Skin - cytology; metabolism; virology Transfection Transforming Growth Factor beta - biosynthesis; genetics beta-Galactosidase - biosynthesis

Associated Chemicals: BMP7 protein, human (0) ; Bone Morphogenetic Protein 7 (0) ; Bone Morphogenetic Proteins (0) ; Transforming Growth Factor beta (0) ; beta-Galactosidase (EC 3.2.1.23)

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