Local OPG gene transfer to periodontal tissue inhibits orthodontic tooth movement.
Previously, we discovered that RANKL expression is induced in compressed periodontal ligament cells, and that this promotes osteoclastogenesis on the compression side in orthodontic tooth movement. We hypothesized that local OPG gene transfer to the periodontium would neutralize the RANKL activity induced by mechanical compressive force, thereby inhibiting osteoclastogenesis and diminishing tooth movement. The upper first molars of six-week-old male Wistar rats were moved palatally by means of a fixed-orthodontic wire. A mouse OPG expression plasmid [pcDNA3.1(+)-mOPG] was constructed, and the production of functional OPG protein was confirmed in vitro. The inactivated HVJ envelope vector containing pcDNA3.1(+)-mOPG or PBS was injected periodically into the palatal periodontal tissue of upper first molars. When this local OPG gene transfer was performed, OPG production was induced, and osteoclastogenesis was inhibited. Local OPG gene transfer significantly diminished tooth movement. In this study, we report that OPG gene transfer to periodontal tissue inhibited RANKL-mediated osteoclastogenesis and inhibited experimental tooth movement.
Kanzaki
H
H
Division of Orthodontics and Dentofacial Orthopedics, Department of Oral Health and Development Sciences, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. kanzaki@mail.tains.tohoku.ac.jp
Chiba
M
M
Takahashi
I
I
Haruyama
N
N
Nishimura
M
M
Mitani
H
H
D000818:Animals; D015519:Bone Density / Q000235:genetics; D001862:Bone Resorption / Q000235:genetics; D002352:Carrier Proteins / Q000502:physiology; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics*; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000502:physiology; D041681:NIH 3T3 Cells; D010010:Osteoclasts / Q000502:physiology; D053244:Osteoprotegerin; D010519:Periodontium / Q000502:physiology*; D010957:Plasmids / Q000235:genetics; D053245:RANK Ligand; D051381:Rats; D017208:Rats, Wistar; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D014087:Tooth Movement Techniques; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D002352:Carrier Proteins; D006023:Glycoproteins; D008024:Ligands; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C506032:Tnfrsf11b protein, rat; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha