The endothelin system mediates bone modeling in the late stage of orthodontic tooth movement in rats

The endothelin system is involved in orthodontic tooth movement (OTM). The aim of the study was to examine the role of ET-1, ETA and ETB in bone modeling during OTM in rats. Male Wistar rats (n = 62) were divided into three groups: control animals (n = 10; control group) without appliance, and two groups of experimental animals, which were applied a super-elastic closed-coil spring between the first left maxillary molar and the incisors and were treated daily with either TBC3214 (n = 10; TBC3214 group) or with saline (n = 42; appliance only group). TBC3214 is a highly selective antagonist on ETA receptors. The distance between teeth was measured on days 0 and 42. On days 0, 14, 28 and 42 animals of the appliance only group (n = 8) were sacrificed and tissue samples were taken. Total RNA and protein contents were isolated. Gene expression levels of ET-1, ETA and ETB were assessed by means of relative RT-PCR. Protein levels of ETA and ETB were examined by immunoblotting. Ten animals of each group were sacrificed on day 42 and tissue samples were prepared for histological analysis. Alveolar bone volume, osteoblast and osteoclast volume were determined histomorphometrically. Gene expression levels of ET-1, ETA and ETB varied throughout the experiment and were significantly up-regulated on day 42 (p < 0.001). The immunoreactivity of ETA and ETB significantly decreased on day 14 (p < 0.001) and increased on day 28 (p < 0.001). Alveolar bone volume was significantly higher in the TBC3214 group compared to the appliance only group (p < 0.001). Osteoclast volume was significantly lower in the TBC3214 group compared to the appliance only group (p < 0.05). Gene and protein expression levels of ET-1, ETA and ETB varied significantly during OTM, suggesting their different roles in the various stages of OTM. TBC3214 significantly increased alveolar bone volume and significantly decreased osteoclast volume, indicating that it decreased bone resorption in stage three of OTM. These data suggest that ET-1 increases osteoclastic bone resorption via ETA in the late stage of OTM.