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

Abstract

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.

Elucidating timing and function of endothelin-A receptor signaling during craniofacial development using neural crest cell-specific gene deletion and receptor antagonism

“…To better define the exact timing of Ednra action, we took a second approach, in which Ednra signaling was blocked for short periods during development using an Ednra-specific antagonist (Padilla et al, 2006; Sprogar et al, 2007). The antagonist, TBC3214 (Encysive Pharmaceuticals), is an orally-bioavailable non-peptidic antagonist with a sub-nanomolar IC 50 (Wu et al, 2001).…”

“…First, we have used a mouse strain carrying a conditional mutation in the Ednra gene (Kedzierski et al, 2003), and crossed these mice with two Cre transgenic mouse lines in which Cre expression in NCCs occurs between E8.25 and E9.5. In a second approach, we have used an Ednra-specific antagonist (Padilla et al, 2006; Sprogar et al, 2007; Wu et al, 2001) to knockdown Ednra signaling at specific time periods of NCC development. Our results indicate that Ednra signaling is required for NCC development in a very narrow temporal window spanning approximately 18 h. In addition, detailed analysis of aberrant craniofacial structures observed following reduction in Ednra signaling in both strains suggest a role for Ednra signaling in the evolution of the mammalian hearing apparatus.…”

Tooth Movement After Infrared Laser Phototherapy: Clinical Study in Rodents

“…2,5,7,8,10,13,[26][27][28] For the orthodontic movement to be efficient, some variables are essential, including the magnitude and duration of the force and the morphology and alveolar bone density. 1 In our study, the initial force (40 g/F) was applied continuously to induce more tooth movement.…”

Cetirizine, a histamine H1 receptor antagonist, decreases the first stage of orthodontic tooth movement in rats

“…In Group III (n = 7) no appliance was used and the rats were treated daily with saline (1 ml/kg i.p.). A superelastic closed coil spring (25 cN, wire diameter 0.15 mm, GAC International, New York, USA) was placed between the fi rst maxillary molar and the incisors [5]. It was fi xed to the upper left fi rst molar with a stainless steel ligature wire (diameter 0.25 mm, Dentaurum, Ispringen, Germany) and to the incisors by surgical steel wire (4-0, multifi lament, W310, Ethicon, Johnson&Johnson, New Jersey, USA).…”