Li Yong, Decker Sylvia, Yuan Zhi-An, Denbesten Pamela K, Aragon Melissa A, Jordan-Sciutto Kelly, Abrams William R, Huh Jung, McDonald Celeste, Chen Enhong, MacDougall Mary, Gibson Carolyn W
Department of Anatomy and Cell Biology, University of Pennsylvania School of Dental Medicine, Philadelphia, 19104-6030, USA.
Arch Oral Biol. 2005 Aug;50(8):681-8. doi: 10.1016/j.archoralbio.2004.11.021. Epub 2005 Feb 1.
Fluoride is associated with a decrease in the incidence of dental caries, but excess fluoride can lead to enamel fluorosis, a defect that occurs during tooth enamel formation. In fibroblasts, the Arhgap gene encodes a RhoGAP, which regulates the small G protein designated RhoA. Fluoride treatment of fibroblasts inactivates RhoGAP, thereby activating RhoA, which leads to elevation of filamentous actin (F-actin). Since RhoA is a molecular switch, our hypothesis is that in ameloblasts, fluoride may alter the cytoskeleton through interference with the Rho signaling pathway. Our objective was to measure the effects of sodium fluoride on F-actin using tooth organ culture and confocal microscopy. The results indicated that cellular responses to fluoride include elevation of F-actin in ameloblasts. It was concluded from immunohistochemistry, RT-PCR and confocal approaches that the components of the Rho pathway are present in ameloblasts, and that the response to fluoride involves the Rho/ROCK pathway.
氟化物与龋齿发病率的降低有关，但过量的氟化物会导致牙釉质氟中毒，这是一种在牙釉质形成过程中出现的缺陷。在成纤维细胞中，Arhgap基因编码一种RhoGAP，它调节名为RhoA的小G蛋白。用氟化物处理成纤维细胞会使RhoGAP失活，从而激活RhoA，导致丝状肌动蛋白（F-肌动蛋白）升高。由于RhoA是一个分子开关，我们的假设是，在成釉细胞中，氟化物可能通过干扰Rho信号通路来改变细胞骨架。我们的目的是使用牙器官培养和共聚焦显微镜来测量氟化钠对F-肌动蛋白的影响。结果表明，细胞对氟化物的反应包括成釉细胞中F-肌动蛋白的升高。通过免疫组织化学、逆转录聚合酶链反应和共聚焦方法得出的结论是，Rho途径的成分存在于成釉细胞中，并且对氟化物的反应涉及Rho/ROCK途径。
