Local osteoprotegerin gene transfer to periodontal tissue inhibits lipopolysaccharide‐induced alveolar bone resorption

Abstract

Osteoclastogenesis is primarily activated by receptor activator of nuclear factor kappaB ligand (RANKL) and is inhibited by osteoprotegerin (OPG). A previous study demonstrated that local OPG gene transfer to periodontal tissue inhibited RANKL-mediated osteoclastogenesis and experimental tooth movement. In the present study, we tested the hypothesis that local OPG gene transfer to the periodontium can neutralize RANKL activity induced by lipopolysaccharide injection, thereby inhibiting osteoclastogenesis and diminishing alveolar bone resorption in experimental periodontal disease. Seven-week-old male Wistar rats received an injection of lipopolysaccharide or phosphate-buffered saline in the palatal gingiva of the upper first molars on both the right and left sides. An inactivated haemagglutinating virus of Japan (HVJ) envelope vector containing a mouse OPG expression plasmid [pcDNA3.1(+)-mOPG] or mock vector was injected periodically into the palatal periodontal tissue of the upper first molars. Lipopolysaccharide injection induced severe periodontal bone resorption. Local OPG gene transfer induced OPG production, and osteoclastogenesis was inhibited. Local OPG gene transfer significantly decreased alveolar bone resorption. Osteoprotegerin gene transfer to periodontal tissue inhibited osteoclastogenesis and alveolar bone resorption in lipopolysaccharide-induced experimental periodontal disease.