The Effect of Radiotherapy on Enamel Associated Proteins

描述（由申请人提供）：本提案是Jacob D. McGuire，DDS为露丝L Kirschstein国家研究服务奖（NRSA）个人博士后研究员（F-32）。该奖项将作为完成他在密苏里大学堪萨斯城牙科学院跨学科口腔生物学博士课程的博士教育的平台。此外，该奖项将使他成为一名独立的牙科研究人员，从事高影响力的研究事业。该提案的总体目标是表征放疗对釉质相关蛋白的影响。大多数口腔癌患者接受放射治疗，以达到抗癌和挽救生命的效果。照射后，出现了许多负面的口腔后遗症，包括牙釉质损失/剪切。病理性牙釉质损失大大降低了患者的生活质量，限制了日常活动的表现; 并对一个人的心理和社会福祉产生负面影响。釉质损失/剪切在放射治疗后开始，并随着时间的推移而进展，导致釉质从支持牙本质部分至完全分层。没有保护性釉质，暴露的牙本质迅速腐烂并导致进一步的发病率。牙釉质相关蛋白是牙釉质发育过程中的残留物，高度集中在切牙、牙尖、牙颈和牙裂区域的牙本质-牙釉质连接处（DEJ）。基于它们在釉质内的位置，它们可以通过赋予DEJ和釉质本身稳定性而充当“粘结材料”。一个机制来解释为什么釉质剪切在正常稳定的交界处的DEJ放疗后尚未阐明。一个可能的解释可能与牙釉质蛋白大量集中在DEJ附近有关。我们推测，放疗可能会改变或破坏蛋白质与釉质改变其结构完整性和化学概况。这些结构和化学变化可能会影响DEJ的稳定性，导致临床观察到的釉质损失。具体目标是：1）表征放疗前和放疗后釉质相关蛋白的结构完整性; 2）表征放疗前和放疗后釉质相关蛋白的化学特征。拟议研究的结果有可能开始定位导致放疗后牙釉质丧失的机制，这将为开始指导放疗后患者预防和恢复治疗的开发提供重要知识。

DESCRIPTION (provided by applicant): This proposal is an initial submission from Jacob D. McGuire, DDS for the Ruth L Kirschstein National Research Service Award (NRSA) for Individual Postdoctoral Fellows (F-32). This award will serve as the platform to complete his doctoral education in the interdisciplinary Oral Biology PhD program at the University of Missouri-Kansas City School of Dentistry. In addition, this award will equip him for a high impact research career as an independent dental researcher. The overall goal of this proposal is to characterize the effect of radiotherapy on enamel associated proteins. The majority of oral cancer patients receive radiotherapy for its anti-cancer and life saving effects. Following irradiation numerous negative oral sequelae develop including enamel loss/shearing. Pathologic enamel loss greatly diminish a patient's quality of life, limit performance of everyday activities; and negatively affect one's psychological and social well-being. Enamel loss/shearing initiates following radiotherapy and progresses over time resulting in partial to complete delamination of enamel from the supporting dentin. Without the protective enamel, exposed dentin decays rapidly and leads to further morbidity. Enamel associated proteins are remnants from developing enamel and are highly concentrated at the dentin-enamel junction (DEJ) in the incisal, cuspal, cervical, and fissure regions. Based on their intraenamel location, they may act as a 'cementing material' by imparting stability to the DEJ and enamel proper. A mechanism to explain why enamel shears at the normally stable junction of the DEJ following radiotherapy has not been elucidated. A potential explanation could be linked to enamel proteins heavily concentrated near the DEJ. We hypothesize that radiotherapy may alter or damage proteins associated with enamel by altering their structural integrity and chemical profile. These structural and chemical changes may affect the stability of the DEJ, resulting in enamel loss observed clinically. The specific aims will 1) characterize the structural integrity of enamel associated proteins before and subsequent to radiotherapy; 2) characterize the chemical profile of enamel associated proteins before and subsequent to radiotherapy. Outcomes of the proposed study have the potential to begin localizing a mechanism contributing to post-radiotherapy enamel loss, which would provide vital knowledge to begin directing development of preventative and restorative treatments for patients post-radiotherapy.