Induction of reparative dentin formation by ultrasound-mediated gene delivery of growth/differentiation factor 11.
Bone morphogenetic proteins (BMPs) are morphogens implicated in embryonic and regenerative odontogenic differentiation. Gene therapy has the potential to induce reparative dentin formation for potential pulp capping. We have optimized the gene transfer of Growth/differentiation factor 11 (Gdf11)/Bmp11 plasmid DNA into dental pulp stem cells by sonoporation in vivo. Dental pulp tissue treated with plasmid pEGFP or CMV-LacZ in 5-10% Optison (Molecular Biosystems Inc., San Diego, CA) and stimulated by ultrasound (1 MHz, 0.5 W/cm(2), 30 sec) showed significant efficiency of gene transfer and high level of protein production selectively in the local region, within 500 microm of the amputated site of the pulp tissue. The Gdf11 cDNA plasmid transferred into dental pulp tissue by sonoporation in vitro, induced the expression of dentin sialoprotein (Dsp), a differentiation marker for odontoblasts. The transfection of Gdf11 by sonoporation stimulated a large amount of reparative dentin formation on the amputated dental pulp in canine teeth in vivo. These results suggest the possible use of BMPs using ultrasound-mediated gene therapy for endodontic dental treatment.
Nakashima
Misako
M
Department of Clinical Oral Molecular Biology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan. misako@dent.kyushu-u.ac.jp
Tachibana
Katsuro
K
Iohara
Koichiro
K
Ito
Masataka
M
Ishikawa
Masaki
M
Akamine
Akifumi
A
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D003782:Dental Pulp / Q000033:anatomy & histology / Q000254:growth & development; D003804:Dentin / Q000502:physiology*; D003810:Dentinogenesis; D004285:Dogs; D016326:Extracellular Matrix Proteins; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D055412:Growth Differentiation Factors; D009804:Odontoblasts / Q000378:metabolism; D009924:Organ Culture Techniques; D010750:Phosphoproteins; D010957:Plasmids; D012038:Regeneration / Q000502:physiology; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D013552:Swine; D014162:Transfection / Q000379:methods*; D014465:Ultrasonics; D000099311:Dentin Sialophosphoprotein
D019485:Bone Morphogenetic Proteins; D016326:Extracellular Matrix Proteins; D055412:Growth Differentiation Factors; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C492266:GDF11 protein, human