Expression levels of endothelin-1, endothelin-2, and endothelin-3 vary during the initial, lag, and late phase of orthodontic tooth movement in rats

Endothelins (ET)-1, ET-2, and ET-3 are one group of cytokines likely to be released during orthodontic tooth movement (OTM). Therefore, the expression of ET levels was investigated to determine the importance and involvement of isopeptides during the several phases of OTM. Thirty-two male Wistar rats (12-13 weeks old) were divided into four groups of eight: control, 14, 28, and 42 day groups. Tooth movement was induced by a closed-coil spring inserted between the upper left first molar and the upper incisors. The distance between the teeth was measured on days 0, 2, 7, 14, 21, 28, 35, and 42 using a digital calliper. The rate of tooth movement was calculated. The animals were sacrificed on days 14, 28, and 42 and gene expression levels of all three ET were determined using reverse transcription polymerase chain reaction. Statistical analysis was performed using two-way analysis of variance, Bonferroni's correction, and paired t-tests. The distance between the teeth decreased in all appliance groups (P < 0.001). The rate of tooth movement was 0.20 +/- 0.02, 0.03 +/- 0.01, and 0.06 +/- 0.02 mm/day between days 0-2, 3-21, and 22-42, respectively. On day 14, gene expression levels for ET-1 (P < 0.05) and ET-3 (P < 0.001) increased compared with day 0. On day 28, a downregulation of ET-3 was observed when compared with day 0 (P < 0.001). On day 42, ET-1 (P < 0.001) and ET-3 (P < 0.01) gene expression levels were strongly upregulated, while ET-2 gene expression level was downregulated (P < 0.01) when compared with day 0. ET-1 and ET-3, but not ET-2, are involved in all three phases of OTM, and ET-1 seems to be the predominant form in the late phase of OTM.