Development of novel therapeutic approach for the prevention of alveolar bone destruction and atherosclerosis through the regulation of Wnt signaling

NF κ B B配体受体激活因子（RANKL）刺激破骨细胞分化，骨保护素（OPG）抑制破骨细胞生成。OPG缺陷小鼠表现出严重的骨硬化和动脉粥样硬化。WNT信号调节细胞分化和/或增殖，并且WNT信号的激活刺激OPG表达。本研究旨在检测RANKL和OPG在牙周炎和动脉粥样硬化病变中的表达，探讨牙周炎在动脉粥样硬化中的作用。此外，Wnt信号通路对OPG表达的影响也被检测用于可能的牙周炎和动脉粥样硬化的治疗方法。目前的研究表明RANKL在牙周炎组织和腹主动脉瘤（AAA）组织中表达增强。在AAA组织中，经常检测到牙周致病菌，但它们在健康组织中完全不存在。牙周致病菌LPS刺激血管平滑肌细胞RANKL表达，RANKL增加MMP表达。这些结果表明，RANKL的表达不仅增加破骨细胞的生成，但AAA病变。通过siRNA抑制Wnt信号传导抑制了各种细胞中的OPG表达。姜黄素增加OPG在各种类型的细胞中的表达，表明它们可能抑制牙周炎和AAA中RANKL的表达。这些结果表明，Wnt信号的调节可能抑制牙周炎和AAA。

Receptor activator of NF kappa B Ligand (RANKL) stimulates osteoclast differentiation, and osteoprotegerin (OPG) suppress the osteoclastogenesis. The OPG deficient mice showed severe osteopetrosis and atherosclerosis. The WNT signaling regulates cell differentiation and/or proliferation, and the activation of WNT signaling stimulates OPG expression. The purpose of this study was to examine the RANKL and OPG expression in periodontitis and atherosclerosis lesions, and evaluate the roles of periodontal infection on atherosclerosis. In addition, effects of Wnt signaling on OPG expression were also examined for the possible therapeutic approach against periodontitis and atherosclerosis. Present study showed that RANKL expression was augmented in periodontitis tissue and abdominal aortic aneurisms (AAA) tissue. In AAA tissues, periodontopathic bacteria were frequently detected, but they were completely absent in the healthy tissues. LPS from periodontopathic bacteria stimulated RANKL expression and RANKL augment MMP expression in vascular smooth muscle cells in vitro. These results suggest that RANKL expression augmented not only osteoclastogenesis, but also AAA lesion. Suppression of Wnt signaling by siRNA suppressed OPG expression in various cells. Curcumin augmented OPG expression in various cell types, suggesting that they might suppress RANKL expression in periodontitis and AAA. These results suggested that regulation of Wnt signaling might suppress periodontitis and AAA.