The effect of adipokines and obesity on periodontal destruction and regeneration

已有强有力的证据表明牙周炎与肥胖有关。在肥胖患者中，许多脂肪因子的血清水平会发生变化，这些脂肪因子是来自脂肪组织的细胞因子。脂肪因子调节食物摄入和能量消耗，但也调节炎症和伤口愈合过程。牙釉质基质衍生物(EMD)和骨形态发生蛋白2(BMP2)可诱导牙周组织再生愈合。目前尚不清楚脂肪因子是否会干扰EMD或BMP2的作用。我们建议在体外和体内研究脂肪因子和肥胖对牙周破坏和再生的影响。具体地说，我们的目标是研究：(I)脂肪因子在体外对炎症、缺氧、生物力学和再生信号的调节；(Ii)脂肪因子在存在和不存在EMD或BMP2的情况下是否以及在多大程度上调节PDL细胞的功能；以及(Iii)脂肪因子分别与EMD和BMP2潜在相互作用的细胞内信号通路。此外，我们将通过在动物模型中检测肥胖对牙周再生的影响来扩展体外研究结果。这些实验将有助于阐明脂肪因子和肥胖在牙周破坏和再生中的作用。

Strong evidence has accumulated that periodontitis is associated with obesity. In obese patients, serum levels of a number of adipokines, which are cytokines derived from adipose tissue, are altered. Adipokines regulate food intake and energy expenditure, but also inflammatory and wound healing processes. Periodontal regenerative healing can be induced by enamel matrix derivative (EMD) and bone morphogenetic protein 2 (BMP2). Whether adipokines interfere with the actions of EMD or BMP2 is as yet unknown. We propose to study the effects of adipokines and obesity on periodontal destruction and regeneration in vitro and in vivo. Specifically, we aim to examine: (i) the regulation of adipokines in human periodontal ligament (PDL) cells in response to inflammatory, hypoxic, biomechanical and regenerative signals in vitro; (ii) if and to what extent adipokines modulate PDL cell functions in the presence and absence of EMD or BMP2; and (iii) the intracellular signaling pathways underlying the potential interactions of adipokines with EMD and BMP2, respectively. Additionally, we will extend in vitro findings by examining the effects of obesity on periodontal regeneration in an animal model. These experiments will help clarify the role of adipokines and obesity in periodontal destruction and regeneration.