AFM and CFM Study of the Etiology of Fluorosis

描述：无论采用何种治疗方式，如果能够减少氟化物的全身副作用，那么氟化物作为一种牙齿防护剂和公共卫生措施的有效性将会增加。饮用水中氟化物的最佳水平L ppm已经确定，因为它可以使龋齿减少30%-50%，而不会相应地增加氟斑牙，尽管众所周知超过L ppm的水平会带来更大的龋齿减少。氟中毒的生物学病因尚不清楚，尽管可能的机制之一是釉质基质蛋白从釉质表面被破坏，阻碍晶体生长，导致釉质发育不良。这项原子力显微镜和化学力显微镜研究(AFM和CFM)将描述和比较含氟和非含氟釉质晶体与特性良好的釉质蛋白、成釉蛋白、成釉蛋白、釉质蛋白及其切割产物的结合能力。最近的研究已经确定了釉质晶体表面的电荷域，这似乎影响了蛋白质晶体与釉质表面的结合。从釉质发育的不同阶段(分泌期、过渡期和成熟期)获得的釉质晶体的使用将有助于识别晶体表面何时出现电荷域，以及氟化物何时对釉质矿化起主要作用。含氟和非含氟牙釉质晶体的蛋白质结合能力将被关联，并与从晶体中剥离这些蛋白质所需的磷酸盐溶液的浓度进行比较。CFM将使用不同的化学修饰尖端(“功能化尖端”)来检查晶体表面电荷域的存在。电荷域在蛋白质/晶体表面相互作用中的作用将被研究。精细描述的蛋白质及其切割产物可能有助于识别参与晶体结合的蛋白质基序。这些蛋白质对晶体生长的影响也将在原子力显微镜中进行检验。单晶生长已经在原子力显微镜中测量到了。在这项研究中将进行类似的生长测量，即晶体的长度和宽度；还将评估凹坑或山丘的形成。该项目的研究结果不仅将有助于阐明釉质基质蛋白在釉质矿化中的作用，也将为氟中毒的发病机制提供解释。这一解释可能会让人们设计出预防氟化物有害影响的疗法或治疗方法，并在一定程度上给予氟化物，这将导致更大程度的减少龋齿。

DESCRIPTION: The effectiveness of fluoride as a Dental preventive agent and public health measure would be increased if the systemic side effects of fluoride could be reduced, no matter what the mode of therapy. The optimal level of fluoride l ppm in drinking water has been established because it gives a reduction of caries of 30-50% without the corresponding increase in Dental fluorosis, although it is known that levels exceeding l ppm would bring about greater reductions in caries. The biological etiology of fluorosis is not understood, although one of the suggested mechanisms is the impaired removal of enamel matrix proteins from enamel surfaces, which impede crystal growth, leading to hypoplastic defects in enamel. This atomic and chemical force microscopy study (AFM and CFM) will describe and compare the binding capacity of fluorotic and non-fluorotic enamel crystals for the well characterized enamel proteins, amelogenin, ameloblastin, enamelin, and their cleavage products. Recent studies have identified charge domains on the enamel crystal surfaces, which appear to affect protein crystal binding to the enamel surfaces. The use of enamel crystals obtained from various stages (secretory, transition and maturation) of enamel development will help identify when charge domains appear on crystal surfaces and when fluoride has major effect on enamel mineralization. Protein binding capacity of both the fluorotic and non-fluorotic enamel crystals will be correlated and compared with the concentration of a phosphate solution needed to strip these proteins from the crystals. The presence of charge domains on the crystal surfaces will be examined by CFM using different chemically modified tips ("functionalized tips"). The role of the charge domains in protein/crystal surface interactions will be investigated. The exquisitely characterized proteins and their cleavage products may help identify the protein motifs involved in the crystal binding. The effect of these proteins on crystal growth will also be examined in the AFM. Single crystal growth has already measured in the AFM. Similar growth measurements will be made in this study, i.e., in crystal length and width; pit or hillock formation will also be assessed. The outcome of this project will not only shed light on the role the enamel matrix proteins play in enamel mineralization, but also offer an explanation for the cause of fluorosis. This explanation may allow therapies or treatments to be devised that will prevent the deleterious effects of fluoride and let it be administered at levels, which will cause a greater reduction in caries.