Gene therapy of bone morphogenetic protein for periodontal tissue engineering

J Periodontol. 2003 Feb;74(2):202-13. doi: 10.1902/jop.2003.74.2.202.

Abstract

Background: The reconstruction of lost periodontal support including bone, ligament, and cementum is a major goal of therapy. Bone morphogenetic proteins (BMPs) have shown much potential in the regeneration of the periodontium. Limitations of BMP administration to periodontal lesions include need for high-dose bolus delivery, BMP transient biological activity, and low bioavailability of factors at the wound site. Gene transfer offers promise as an alternative treatment strategy to deliver BMPs to periodontal tissues.

Methods: This study utilized ex vivo BMP-7 gene transfer to stimulate tissue engineering of alveolar bone wounds. Syngeneic dermal fibroblasts (SDFs) were transduced ex vivo with adenoviruses encoding either green fluorescent protein (Ad-GFP or control virus), BMP-7 (Ad-BMP-7), or an antagonist of BMP bioactivity, noggin (Ad-noggin). Transduced cells were seeded onto gelatin carriers and then transplanted to large mandibular alveolar bone defects in a rat wound repair model.

Results: Ad-noggin treatment tended to inhibit osteogenesis as compared to the control-treated and Ad-BMP-7-treated specimens. The osseous lesions treated by Ad-BMP-7 gene delivery demonstrated rapid chrondrogenesis, with subsequent osteogenesis, cementogenesis and predictable bridging of the periodontal bone defects.

Conclusion: These results demonstrate the first successful evidence of periodontal tissue engineering using ex vivo gene transfer of BMPs and offers a new approach for repairing periodontal defects.

Publication types

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

MeSH terms

  • Adenoviridae
  • Alkaline Phosphatase / metabolism
  • Alveolar Bone Loss / therapy*
  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins / administration & dosage*
  • Bone Regeneration / drug effects*
  • Carrier Proteins
  • Cell Division
  • Cells, Cultured
  • Cementogenesis / drug effects
  • Cloning, Molecular
  • Fibroblasts
  • Genetic Therapy / methods*
  • Immunohistochemistry
  • Protein Biosynthesis
  • Proteins*
  • Rats
  • Tissue Engineering / methods*
  • Transduction, Genetic*
  • Transforming Growth Factor beta*

Substances

  • Bmp7 protein, rat
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • Carrier Proteins
  • Proteins
  • Transforming Growth Factor beta
  • noggin protein
  • Alkaline Phosphatase