Salivary Biomarkers to Predict Alveolar Bone Loss

描述：该R21应用程序的目标是开发一种客观，快速的系统，可以轻松地用于牙科！以确定患者在未来牙槽骨丢失的高风险。这些信息将使医生能够针对最需要治疗的患者进行适当的干预，并避免对这些服务需求有限的患者进行昂贵和耗时的治疗。我们将利用一种已建立的方法，该方法使用涂有特异性抗体的顺磁性微球来捕获、检索、浓缩和鉴定与唾液中牙周骨破坏相关的生物标志物。本研究的一般假设是，来自人唾液的宿主来源的骨吸收因子如白细胞介素-1-β（IL-1-β）、肿瘤坏死因子-α（TNF α）、白细胞介素-6（IL-6）和前列腺素E2（PGE 2）将作为活性骨破坏的生物标志物。此外，我们还将使用该技术来浓缩骨破坏的产物，例如I型胶原蛋白的C-端肽吡啶啉交联（ICTP），骨钙素和人唾液中的骨连接素。然后使用简单的比色法对这些浓缩产品进行定量。这些生物标志物，所有这些先前已被报道在患有活动性牙周病的受试者的龈沟液（GCF）中升高，连同其他众所周知的风险因素，例如年龄、烟草使用等，将用于开发预测未来牙槽骨丢失的统计诊断模型，纵向监测患者的任何PD状态变化，并评估治疗成功或失败。 使用磁性微球来定量唾液中的生物标志物具有若干优点。微球允许浓缩可能存在于唾液中的少量生物标志物。微球也可以用具有多种特异性的抗体包被，这将允许同时定量来自同一唾液样品的多种靶生物标志物。与GCF不同，唾液很容易获得，并且可以以最小的努力快速收集。我们设想，这种方法可以方便地适应在未来使用的执业牙医提供客观的信息，以评估牙周骨丢失的风险。

DESCRIPTION: The goal of this R21 application is to develop an objective, rapid system that can be used with ease in the dental! office to identify patients at high risk for future alveolar bone loss. This information will allow the practitioner to target appropriate interventions to patients in most need of treatment and avoid expensive and time consuming treatment for patients having limited need for these services. We will exploit an established method that uses paramagnetic microspheres coated with specific antibodies to capture, retrieve, concentrate and identify biomarkers associated with periodontal bone destruction in saliva in one step. The general hypothesis of this study is that host-derived bone resorptive factors such as interleukin-1-beta(IL-1-beta, tumor necrosis factor-alpha(TNFalpha, interleukin-6 (ll-6), and prostaglandin-E2 (PGE2) from human saliva will serve as biomarkers of active bone destruction. Additionally, we will use this technology to also concentrate products of bone destruction, such as C-telopeptide pyridinoline crosslinks of Type I collagen (ICTP), osteocalcin and osteonectin from human saliva. These concentrated products will then be quantitated using simple colorometric methods. These biomarkers, all of which have been previously reported to be elevated in gingival crevicular fluid (GCF) of subjects with active periodontal disease, in conjunction with other well known risk factors, e.g. age, tobacco use, etc., will be used to develop statistical diagnostic models for predicting future alveolar bone loss, monitoring patients longitudinally with respect to any PD status change and evaluating treatment success or failure. The use of the magnetic microspheres to quantitate biomarkers in saliva has several advantages. The microspheres allow concentration of small amounts of biomarkers that may be present in saliva. The microspheres can also be coated with antibodies with multiple specificities that will allow simultaneous quantitation of multiple target biomarkers from the same saliva sample. Saliva, unlike GCF, is readily accessible and can be rapidly collected with minimal effort. We envision that this approach could be conveniently adapted in the future for use by practicing dentists to provide objective information to assess risk for periodontal bone loss.