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.

Clodronate, a non-N-containing bisphosphonate, strongly inhibits bone resorption and also has anti-inflammatory properties. The purpose of this study was to examine the effect of the local administration of clodronate on orthodontic tooth movement. Both the right and left upper first molars of 26 7-week-old male Wistar rats were moved buccally with a standardized expansion spring. Clodronate solution was injected into the sub-periosteum area adjacent to the left upper molar every third day during the experimental period. The right first molar served as the control. Local injection of clodronate caused a significant (P < 0.001) and dose-dependent reduction in tooth movement in the rats. The number of osteoclasts on the clodronate-injected side was significantly less (P < 0.01) than on the control side. Local clodronate also inhibited root resorption incident to tooth movement. These results suggest that localized use of clodronate could be a useful therapeutic adjunct in orthodontic treatment.