Effect of Angiotensin II Receptor Blocker on Experimental Periodontitis in a Mouse Model of Marfan Syndrome
Effect of Angiotensin II Receptor Blocker on Experimental Periodontitis in a Mouse Model of Marfan Syndrome
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DOI：
10.1128/iai.00886-12
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发表时间：
2013-01-01
影响因子：
3.1
通讯作者：
Ganburged, Ganjargal
中科院分区：
文献类型：
--
作者：
Suda, Naoto;Moriyama, Keiji;Ganburged, Ganjargal
马凡综合征是一种常染色体显性遗传疾病，其特征是主动脉根部动脉瘤和扩张、身材高大、晶状体异位。这些表现反映了转化生长因子β（TGF-β）的过度信号传导。此外，病例常常伴有严重的牙周炎，这是牙龈、牙周膜和牙槽骨的慢性炎症。最近，血管紧张素 II 受体阻滞剂 (ARB) 被发现是一类有效的药物，可以通过抑制 TGF-β 信号传导来预防马凡综合征的主动脉瘤和扩张。为了研究 ARB 对牙周炎进展的影响，在马凡综合征 (Mg Delta) 小鼠模型中检查了强效 ARB 替米沙坦的应用。六周大的雄性杂合 Mg Delta 和野生型小鼠受到牙龈卟啉单胞菌的攻击，牙龈卟啉单胞菌会导致慢性牙周炎，无论是否应用替米沙坦。感染后，通过微型计算机断层扫描（mu CT）测量牙槽骨吸收，并检查炎症细胞因子水平。牙龈卟啉单胞菌的感染诱导了 Mg Delta 和野生型小鼠的牙槽骨吸收。前者的吸收量明显大于后者。免疫阵列和酶联免疫吸附测定 (ELISA) 分析表明，受感染的 Mg Delta 小鼠中白细胞介素 17 (IL-17) 和肿瘤坏死因子 α (TNF-α) 水平显着高于受感染的野生型小鼠。替米沙坦治疗显着抑制了感染 Mg Delta 小鼠的牙槽骨吸收。替米沙坦还显着降低了受感染 Mg Delta 小鼠的 TGF-β、IL-17 和 TNF-α 水平，使其达到受感染野生型小鼠的水平。这项研究表明，ARB 可以预防马凡综合征中常见的严重牙周炎。
Marfan syndrome is an autosomal dominant disease characterized by aneurysm and dilatation of the aortic root, tall stature, and ectopia lentis. These manifestations reflect excessive signaling of transforming growth factor beta (TGF-beta). Moreover, cases are frequently associated with severe periodontitis, which is a chronic inflammation of the gingiva, periodontal ligament, and alveolar bone. Recently, angiotensin II receptor blockers (ARBs) were discovered to be an effective drug class that can prevent aortic aneurysm and dilation in Marfan syndrome by inhibiting TGF-beta signaling. To investigate the effect of ARB on the progression of periodontitis, the application of a potent ARB, telmisartan, was examined in a mouse model of Marfan syndrome (Mg Delta). Six-week-old male heterozygous Mg Delta and wild-type mice were challenged with Porphyromonas gingivalis, which causes chronic periodontitis, with and without telmisartan application. After infection, alveolar bone resorption was measured by micro-computed tomography (mu CT), and inflammatory cytokine levels were examined. Infection of Porphyromonas gingivalis induced alveolar bone resorption in both Mg Delta and wild-type mice. The amount of resorption was significantly larger in the former than the latter. Immunoarray and enzyme-linked immunosorbent assay (ELISA) analyses demonstrated that interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-alpha) levels were significantly higher in infected Mg Delta mice than infected wild-type mice. Telmisartan treatment significantly suppressed the alveolar bone resorption of infected Mg Delta mice. Telmisartan also significantly decreased levels of TGF-beta, IL-17, and TNF-alpha in infected Mg Delta mice to levels seen in infected wild-type mice. This study suggests that ARB can prevent the severe periodontitis frequently seen in Marfan syndrome.