Application of HIF-1α by gene therapy enhances angiogenesis and osteogenesis in alveolar bone defect regeneration

J Gene Med. 2016 Apr;18(4-6):57-64. doi: 10.1002/jgm.2876.

Abstract

Background: A successful clinical outcome for implanted tissue-engineered bone is dependent on the establishment of a functional vascular network. Gene-enhanced tissue engineering represents a promising approach for vascularization and osteogenesis. In the present study, we tested the angiogenesis and osteogenesis efficacy of gelatin as the scaffold carrier in combination with a virus encoding the HIF-1α gene in a rat alveolar bone defect model.

Methods: Three groups of 10 rats each were either left untreated, treated with adenovirus encoding hypoxia-inducible factor-1α (AdHIF-1α)/gelatin sponge or treated with gelatin sponge with adenovirus encoding red fluorescence protein, respectively. At 4 weeks, all samples were determined by micro-computed tomography, histological analyses and immunohistochemical studies.

Results: Scaffolds loaded with AdHIF-1α were able to sustain the release of AdHIF-1α for up to 21 days and alveolar bone defects treated with scaffolds containing AdHIF-1α significantly induced new bone and new vessel formation in vivo.

Conclusions: Overexpression of HIF-1α by gene therapy may be a useful method for enhancing alveolar bone defect osteogenesis and angiogenesis. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: HIF-1α; angiogenesis; bone defect; gene therapy; osteogenesis.

MeSH terms

  • Adenoviridae / genetics
  • Alveolar Bone Loss / genetics*
  • Alveolar Bone Loss / physiopathology
  • Alveolar Bone Loss / therapy
  • Animals
  • Bone Regeneration / genetics*
  • Cells, Cultured
  • Genetic Therapy / methods
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Male
  • Neovascularization, Physiologic / genetics*
  • Osteogenesis / genetics*
  • Rats, Sprague-Dawley
  • Time Factors
  • Tissue Engineering / methods
  • X-Ray Microtomography

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit