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

J Cell Biochem. 2000 Jun 6;78(3):476-86. doi: 10.1002/1097-4644(20000901)78:3<476::aid-jcb12>;2-5.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / metabolism*
  • Animals
  • Blotting, Western
  • Bone Development*
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins / biosynthesis*
  • Bone Morphogenetic Proteins / genetics
  • Bone and Bones / cytology
  • Bone and Bones / metabolism*
  • Bone and Bones / virology
  • COS Cells / metabolism
  • COS Cells / virology
  • Cattle
  • Cells, Cultured
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Fibroblasts / virology
  • Gene Expression
  • Genetic Therapy*
  • Genetic Vectors
  • Humans
  • In Vitro Techniques
  • Mice
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / virology
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Osteoblasts / virology
  • Osteogenesis*
  • Skin / cytology
  • Skin / metabolism
  • Skin / virology
  • Transfection
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / genetics
  • beta-Galactosidase / biosynthesis


  • BMP7 protein, human
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • Transforming Growth Factor beta
  • beta-Galactosidase