The effects of TBC3214, a selective endothelin ETA receptor antagonist, on orthodontic tooth movement in rats

Many chemical messengers are involved in the process of alveolar bone and periodontal ligament remodelling during orthodontic tooth movement. Among them is probably endothelin-1 (ET-1). Its role in this process has been partly explained using tezosentan, which affects endothelin A (ET(A)) and endothelin B (ET(B)) receptors. Tezosentan enhances orthodontic tooth movement. The aim of this study was to determine the possible effects of a highly selective ET(A) antagonist on orthodontic tooth movement in rats. Thirty male Wistar rats, 11-12 weeks of age, divided into three equal groups. In group I, a closed-coil spring was used and they were treated daily with 15 mg/kg body weight of TBC3214, a highly selective ET(A) antagonist. A closed-coil spring was also used in group II and the animals were treated daily with a placebo. Group III were treated daily with a placebo. The coil spring delivered a force of 25 cN and was attached between the upper left first molar and upper left incisor. The distance between the teeth was measured with a digital calliper (accuracy +/- 0.01 mm) on days 0, 7, 14, 21, 24, 32, 37, and 40. The differences in the distance between the teeth were calculated to determine the amount of tooth movement. Statistical analysis was performed using two-way analysis of variance, Bonferroni's correction, and paired t-tests. The distance between the upper left first molar and the upper left incisor decreased in groups I and II. In group I, tooth movement was significantly less on days 32 and 37 (P < 0.01) and on day 40 (P < 0.001) compared with group II. In group III, the distance between the teeth increased during the study (P < 0.001). In animals treated daily with TBC3214, tooth movement was significantly less compared with the animals treated with a placebo. It is concluded that ET-1, which is the predominant form of endothelin isopeptides, is involved in orthodontic tooth movement in rats, probably by enhancing bone resorption via ET(A) receptors.