Gene therapy of bone morphogenetic protein for periodontal tissue engineering.
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.


CONCLUSIONS
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.
Jin
Q M
QM
Center for Craniofacial Regeneration, School of Dentistry, University of Michigan, Ann Arbor, MI 48109-1078, USA.
Anusaksathien
O
O
Webb
S A
SA
Rutherford
R B
RB
Giannobile
W V
WV
D000256:Adenoviridae; D000469:Alkaline Phosphatase / Q000378:metabolism; D016301:Alveolar Bone Loss / Q000628:therapy*; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D001861:Bone Regeneration / Q000187:drug effects*; D002352:Carrier Proteins; D002455:Cell Division; D002478:Cells, Cultured; D025021:Cementogenesis / Q000187:drug effects; D003001:Cloning, Molecular; D005347:Fibroblasts; D015316:Genetic Therapy / Q000379:methods*; D007150:Immunohistochemistry; D014176:Protein Biosynthesis; D011506:Proteins; D051381:Rats; D023822:Tissue Engineering / Q000379:methods*; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein
D000469:Alkaline Phosphatase; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D011506:Proteins; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein; C525821:Bmp7 protein, rat