Induction of dental pulp stem cell differentiation into odontoblasts by electroporation-mediated gene delivery of growth/differentiation factor 11 (Gdf11).
The long-term goal of dental treatment is to preserve teeth and prolong their function. In dental caries an efficient method is to cap the exposed dental pulp and conserve the pulp tissue with reparative dentin. We examined whether growth/differentiation factor 11 (GDF11), a morphogen could enhance the healing potential of pulp tissue to induce differentiation of pulp stem cells into odontoblasts by electroporation-mediated gene delivery. Recombinant human GDF11 induced the expression of dentin sialoprotein (Dsp), a differentiation marker for odontoblasts, in mouse dental papilla mesenchyme in organ culture. The Gdf11 cDNA plasmid which was transferred into mesenchymal cells derived from mouse dental papilla by electroporation, induced the expression of Dsp. The in vivo transfer of Gdf11 by electroporation stimulated the reparative dentin formation during pulpal wound healing in canine teeth. These results provide the scientific basis and rationale for gene therapy for endodontic treatments in oral medicine and dentistry.
Nakashima
M
M
Department of Clinical Oral Molecular Biology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
Mizunuma
K
K
Murakami
T
T
Akamine
A
A
D000818:Animals; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002454:Cell Differentiation; D003481:Cuspid; D003731:Dental Caries / Q000628:therapy*; D003782:Dental Pulp / Q000166:cytology* / Q000378:metabolism; D004285:Dogs; D018274:Electroporation; D015316:Genetic Therapy / Q000379:methods*; D055412:Growth Differentiation Factors; D017403:In Situ Hybridization; D051379:Mice; D009804:Odontoblasts / Q000378:metabolism; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; C492266:GDF11 protein, human; C119153:Gdf11 protein, mouse; D055412:Growth Differentiation Factors; D012333:RNA, Messenger; D012795:Sialoglycoproteins