Stimulation of new bone formation by direct transfer of osteogenic plasmid genes.

• J Fang

  Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109, USA.

• Y Y Zhu

  Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109, USA.

• E Smiley

  Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109, USA.

• J Bonadio

  Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109, USA.

• J P Rouleau

  Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109, USA.

• S A Goldstein

  Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109, USA.

• L K McCauley

  Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109, USA.

• B L Davidson

  Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109, USA.

• B J Roessler

  Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109, USA.

抄録

Degradable matrices containing expression plasmid DNA [gene-activated matrices (GAMs)] were implanted into segmental gaps created in the adult rat femur. Implantation of GAMs containing beta-galactosidase or luciferase plasmids led to DNA uptake and functional enzyme expression by repair cells (granulation tissue) growing into the gap. Implantation of a GAM containing either a bone morphogenetic protein-4 plasmid or a plasmid coding for a fragment of parathyroid hormone (amino acids 1-34) resulted in a biological response of new bone filling the gap. Finally, implantation of a two-plasmid GAM encoding bone morphogenetic protein-4 and the parathyroid hormone fragment, which act synergistically in vitro, caused new bone to form faster than with either factor alone. These studies demonstrate for the first time that repair cells (fibroblasts) in bone can be genetically manipulated in vivo. While serving as a useful tool to study the biology of repair fibroblasts and the wound healing response, the GAM technology may also have wide therapeutic utility.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 93 (12), 5753-5758, 1996-06-11

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1363951796120459648
• NII論文ID: 80009034654
• DOI: 10.1073/pnas.93.12.5753
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.93.12.5753
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