PPARs and periodontal disease

 描述(申请人提供)：牙龈卟啉单胞菌(Pg)是牙周的一种重要病原体。控制牙周病原体引起的慢性炎症被认为是减轻以牙周病(PD)为特征的软硬组织破坏的核心。中到重度帕金森病患者的临床治疗通常需要高度侵入性的方法。因此，寻求开发非侵入性措施来治疗性地调节病原体驱动的炎症和限制口腔骨丢失，以增加目前帕金森病的临床治疗方式。最近的研究表明，一组核激素受体，即过氧化物酶体增殖物激活受体(PPAR)，作为潜在的治疗分子，已被证明控制与炎症相关的基因的表达。尽管存在一些关于PPAR在病原体诱导的炎症中所起作用的支持性数据，但在PD相关细菌感染引发的炎症和口腔骨丢失方面，我们的知识存在着显著的差距。根据我们的初步数据，以及利用PPAR作为控制PG感染引起的炎症和口腔骨丢失的治疗靶点的知识空白，我们认为PPAR控制关键炎症因子的表达，这些炎症因素导致炎症和由已定义的牙周病原体PG引起的口腔骨丢失。我们的方法将利用体外筛选，使用人类组织驻留的巨噬细胞和上皮细胞来确定PPAR激动剂或拮抗剂，该激动剂或拮抗剂最显著地降低对PG挑战的细胞炎症反应。然后，这种PPAR靶向分子将在动物模型中进行测试，以确定其在减少PG口腔感染引发的炎症和口腔骨丢失方面的治疗价值。

 DESCRIPTION (provided by applicant): Porphyromonas gingivalis (Pg) is a keystone periodontal pathogen. Controlling chronic inflammation elicited by periodontal pathogens is thought central to mitigating soft and hard tissue destruction that characterizes periodontal disease (PD). Clinical treatment of patients with moderate to severe PD typically requires highly invasive approaches. Thus, development of non-invasive measures to therapeutically regulate pathogen-driven inflammation and limit oral bone loss are sought to augment current PD clinical treatment modalities. Recent studies have identified that one group of nuclear hormone receptors, peroxisome proliferator-activated receptors (PPARs), as potential molecules of therapeutic value as PPARs have been shown to control expression of genes involved in inflammation. Although some supportive data exists regarding the role played by PPARs in pathogen- induced inflammation, there is a significant gap in our knowledge in the context of PD-associated bacterial infection-elicited inflammation, and oral bone loss. Based on our preliminary data, and the gap in knowledge regarding specific PPAR exploitation as a therapeutic target for controlling Pg infection-elicited inflammation and oral bone loss, we propose that that PPARs control the expression of key inflammatory elements that contribute inflammation and oral bone loss elicited by the defined periodontal pathogen Pg. Our approach, will utilize an in vitro screen employing human tissue resident macrophages and epithelial cells to identify a PPAR agonist or antagonist that most significantly reduces cellular inflammatory response to Pg challenge. This PPAR-targeting molecule will then be tested in an animal model to define its therapeutic value in reducing Pg oral infection- elicited inflammation and oral bone loss.