Liu Xiao-Li, Li Chang-Cheng, Liu Ke-Jian, Cui Cai-Yan, Zhang Yu-Zeng, Liu Yun
Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hubei Wuhan 430030, People’s Republic of China.
Biol Trace Elem Res. 2012 Jul;148(1):117-21. doi: 10.1007/s12011-012-9333-9.
The effective therapy of fluoride-induced bone diseases requires an understanding of the mechanism of the disorders. Changes in the inhibitors of the Wnt/β-catenin pathway, Dickkopf-1 (Dkk-1) and Sclerostin (SOST),were studied in supernatants harvested from rat skin fibroblasts cultured with varied doses of fluoride. The contents of SOST and Dkk-1 in fibroblast supernatants were assessed at four exposure time-points and investigated by using the method of ELISA. Compared to the relevant controls(0 mg F(−)/L), a significant decrease of the concentrations of SOST and Dkk-1 was observed as the fluoride concentration increased. Compared to the relevant time controls (24 h), a significant decrease of the concentrations of SOST and Dkk-1 was observed with the extension of time. Our results suggest that the Wnt/β-catenin pathway inhibitors Dkk-1 and SOST play an important role in skeletal fluorosis. They can be used as important indications for diagnosing bone metabolism changes caused by fluoride exposure and therapeutic targets in diseases resulting from fluoride exposure.
氟中毒性骨病的有效治疗需要了解这些病症的发病机制。研究了用不同剂量氟培养的大鼠皮肤成纤维细胞收获的上清液中Wnt/β-连环蛋白通路抑制剂Dickkopf-1（Dkk-1）和硬化蛋白（SOST）的变化。在四个暴露时间点评估成纤维细胞上清液中SOST和Dkk-1的含量，并采用酶联免疫吸附测定法进行研究。与相关对照组（0 mg F（−）/L）相比，随着氟浓度的增加，观察到SOST和Dkk-1浓度显著降低。与相关时间对照组（24小时）相比，随着时间延长，观察到SOST和Dkk-1浓度显著降低。我们的结果表明，Wnt/β-连环蛋白通路抑制剂Dkk-1和SOST在氟骨症中起重要作用。它们可作为诊断氟暴露引起的骨代谢变化的重要指标以及氟暴露所致疾病的治疗靶点。
