Effects of Obesity on Periodontal Tissues Subjected to Biomechanical Forces

在过去的几十年里，肥胖在世界范围内一直在增加，并且是许多慢性疾病的主要危险因素。荟萃分析表明，肥胖也与牙周炎有关，牙周炎是一种由细菌引起的牙齿支撑组织炎症性疾病。肥胖的特点是脂肪组织过多，脂肪组织分泌一种叫做脂肪因子的生物活性分子。虽然肥胖对牙周炎的影响及其治疗是当前牙科研究的热点，但肥胖是否也影响牙周组织对生物力学载荷的反应，如正畸牙齿运动或咬合力，在很大程度上被忽视。虽然正畸牙齿运动和咀嚼在牙周健康中是理想的，但由于菌斑控制不足，生物力学负荷组织可能会发生细菌感染。因此，提出的体内和体外项目的主要目的是研究肥胖和脂肪因子在存在和不存在细菌感染的情况下对牙周细胞和组织的生物力学作用的影响。具体来说，在一项体内研究中，在存在和不存在结扎性牙周炎的情况下，将在喂食高脂肪或标准饮食的Holtzman大鼠中进行正畸牙齿运动。随后，将通过显微计算机断层扫描和组织形态学分析牙周组织重塑形态学，并通过蛋白质组学分析研究与炎症、组织代谢和细胞内信号传导相关的分子的蛋白质合成。此外，在体外研究中，牙周细胞将受到生物力学应变和/或牙周病原体牙龈卟啉单胞菌在存在和不存在脂肪因子。随后，将分析与炎症、组织代谢和细胞内信号传导相关的分子，从而扩大体内研究结果，特别关注脂肪因子作为可能的局部肥胖相关病理机制。总之，体内和体外项目将提供关于肥胖和脂肪因子对受生物力学力作用的牙周组织的影响的新颖和重要的信息。通过阐明肥胖对受生物力学载荷影响的牙周组织的作用，揭示所涉及的病理生理事件、分子和信号通路，该临床前项目将为临床随访研究奠定基础，为超重和肥胖个体的正畸治疗开辟新的方案。

Over the past decades, obesity has been increasing worldwide and represents a major risk factor for many chronic diseases. Meta-analyses have demonstrated that obesity is also associated with periodontitis, a bacteria-induced inflammatory disease of the tooth-supporting tissues. Obesity is characterized by excess adipose tissue, which secrets bioactive molecules called adipokines. Although the effects of obesity on periodontitis and its therapy are a hot topic of current dental research, it has been largely neglected if obesity also affects the response of periodontal tissues to biomechanical loading, such as orthodontic tooth movement or occlusal forces. Although orthodontic tooth movement and mastication ideally occur in periodontal health, bacterial infection of the biomechanically loaded tissues can occur due to insufficient plaque control. Therefore, the main objective of the proposed in-vivo and in-vitro projects is to study the effects of obesity and adipokines on the actions of biomechanical forces on periodontal cells and tissues in the presence and absence of bacterial infection. Specifically, in an in-vivo study, orthodontic tooth movement in the presence and absence of ligature-induced periodontitis will be performed in Holtzman rats fed either with high-fat or standard diet. Afterwards, periodontal tissue remodeling will be analyzed morphologically by microcomputed tomography and histomorphometry, and protein synthesis of molecules related to inflammation, tissue metabolism and intracellular signaling will be investigated by proteomic analysis. Additionally, in an in-vitro study, periodontal cells will be subjected to biomechanical strain and/or the periodontopathogen Porphyromonas gingivalis in the presence and absence of adipokines. Subsequently, molecules related to inflammation, tissue metabolism, and intracellular signaling will be analyzed, thereby expanding the in-vivo findings with a special focus on adipokines as a possible local obesity-associated pathomechanism. Together, the in-vivo and in-vitro projects will provide novel and critical information on the effects of obesity and adipokines on periodontium subjected to biomechanical forces. By clarifying the role of obesity on periodontal tissues subjected to biomechanical loading and unraveling pathophysiological events, molecules and signaling pathways involved, the proposed pre-clinical project will serve as a basis for a clinical follow-up study, which may open up new orthodontic treatment protocols in overweight and obese individuals.