title: Intramarrow bone morphogenetic protein 4 gene delivery improves local bone quality in femurs of ovariectomized rabbits.
abstract: BACKGROUND
  Poor bone quality at implant recipient site is a major risk factor for implant failure. The purpose of this study is to examine the potential of intramarrow bone morphogenetic protein 4 (BMP4) gene delivery for local bone quality improvement.
  
  
  METHODS
  Adenoviral vector encoding human BMP4 (Ad-BMP4) was constructed. Adenovirus encoding β-galactosidase (Ad-LacZ) was used as a control virus. Ad-BMP4 and Ad-LacZ were injected into femurs of ovariectomized rabbits. The temporal changes in bone mineral density at injected areas were determined by repeated measurements by dual-energy x-ray absorptiometry at 0, 1, 2, 4, and 8 weeks after injection. The effects of gene delivery on cortical bone and cancellous bone were evaluated by microcomputed tomography analysis and histologic examination at 8 weeks.
  
  
  RESULTS
  The bone mineral density of the BMP4 group was significantly higher than the LacZ group at 4 and 8 weeks by 61% and 35%, respectively. Results from microcomputed tomography analysis and histologic examination at 8 weeks indicated thicker cortical bone and denser cancellous bone in the BMP4 group compared to the LacZ group.
  
  
  CONCLUSIONS
  Intramarrow gene delivery of BMP4 effectively improved local bone quality for at least 8 weeks. The sustained delivery of osteogenic factors via local gene therapy approach may reduce implant failures associated with poor local bone quality.
authors.affiliation: Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wen-Kai
authors.initials: WK
authors.lastname: Hsiao
authors.forename: Tu-Lai
authors.initials: TL
authors.lastname: Yew
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Lai
authors.forename: Shyh-Yuan
authors.initials: SY
authors.lastname: Lee
authors.forename: Hen-Li
authors.initials: HL
authors.lastname: Chen
mesh_terms: D015502:Absorptiometry, Photon; D000256:Adenoviridae; D000818:Animals; D015519:Bone Density / Q000235:genetics*; D001853:Bone Marrow; D055415:Bone Morphogenetic Protein 4 / Q000096:biosynthesis / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D007267:Injections; D051379:Mice; D032446:Myoblasts; D010052:Ovariectomy; D011817:Rabbits; D055114:X-Ray Microtomography
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4