Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany.
PLoS One. 2013;8(1):e54860. doi: 10.1371/journal.pone.0054860. Epub 2013 Jan 23.
Periodontal infections are independent risk factors for atherosclerosis. However, the exact mechanisms underlying this link are yet unclear. Here, we evaluate the in vivo effects of bacteremia with a periodontal pathogen on endothelial progenitors, bone marrow-derived cells capable of endothelial regeneration, and delineate the critical pathways for these effects.
12-week old C57bl6 wildtype or toll-like receptor (TLR)-2 deficient mice were repeatedly intravenously challenged with 10⁹ live P. gingivalis 381 or vehicle. Numbers of Sca1+/flk1+ progenitors, circulating angiogenic cells, CFU-Hill, and late-outgrowth EPC were measured by FACS/culture. Endothelial function was assessed using isolated organ baths, reendothelization was measured in a carotid injury model. RANKL/osteoprotegerin levels were assessed by ELISA/qPCR.
In wildtype mice challenged with intravenous P.gingivalis, numbers of Sca1+/flk1+ progenitors, CAC, CFU-Hill, and late-outgrowth EPC were strongly increased in peripheral circulation and spleen, whereas Sca1+/flk1+ progenitor numbers in bone marrow decreased. Circulating EPCs were functional, as indicated by improved endothelial function and improved reendothelization in infected mice. The osteoprotegerin/RANKL ratio was increased after P. gingivalis challenge in the bone marrow niche of wildtype mice and late-outgrowth EPC in vitro. Conversely, in mice deficient in TLR2, no increase in progenitor mobilization or osteoprotegerin/RANKL ratio was detected.
Recurrent transient bacteremias, a feature of periodontitis, increase peripheral EPC counts and decrease EPC pools in the bone marrow, thereby possibly reducing overall endothelial regeneration capacity, conceivably explaining pro-atherogenic properties of periodontal infections. These effects are seemingly mediated by toll-like receptor (TLR)-2.
牙周感染是动脉粥样硬化的独立危险因素。然而，这种联系的确切机制尚不清楚。在这里，我们评估了牙周病原体菌血症对内皮祖细胞（能够进行内皮再生的骨髓源性细胞）的体内影响，并阐明了这些影响的关键途径。
12 周龄 C57bl6 野生型或 Toll 样受体（TLR）-2 缺陷型小鼠反复静脉内用 10⁹ 活 P. gingivalis 381 或载体进行挑战。通过 FACS/培养测量 Sca1+/flk1+祖细胞、循环血管生成细胞、CFU-Hill 和晚期成血管内皮祖细胞的数量。使用分离的器官浴评估内皮功能，在颈动脉损伤模型中测量再内皮化。通过 ELISA/qPCR 评估 RANKL/骨保护素水平。
在接受静脉内 P.gingivalis 挑战的野生型小鼠中，Sca1+/flk1+祖细胞、CAC、CFU-Hill 和晚期成血管内皮祖细胞的数量在外周循环和脾脏中强烈增加，而骨髓中的 Sca1+/flk1+祖细胞数量减少。循环内皮祖细胞具有功能，因为感染小鼠的内皮功能得到改善，再内皮化得到改善。在野生型小鼠的骨髓龛中和体外晚期成血管内皮祖细胞中，P. gingivalis 挑战后骨保护素/RANKL 比值增加。相反，在 TLR2 缺陷型小鼠中，未检测到祖细胞动员或骨保护素/RANKL 比值增加。
复发性短暂菌血症是牙周炎的一个特征，它增加了外周 EPC 计数，减少了骨髓中的 EPC 池，从而可能降低整体内皮再生能力，这可以解释牙周感染的促动脉粥样硬化特性。这些影响似乎是由 Toll 样受体（TLR）-2 介导的。
