title: Effect of angiotensin II receptor blocker on experimental periodontitis in a mouse model of Marfan syndrome.
abstract: 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-β). 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-β 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 (MgΔ). Six-week-old male heterozygous MgΔ 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 (μCT), and inflammatory cytokine levels were examined. Infection of Porphyromonas gingivalis induced alveolar bone resorption in both MgΔ 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-α) levels were significantly higher in infected MgΔ mice than infected wild-type mice. Telmisartan treatment significantly suppressed the alveolar bone resorption of infected MgΔ mice. Telmisartan also significantly decreased levels of TGF-β, IL-17, and TNF-α in infected MgΔ mice to levels seen in infected wild-type mice. This study suggests that ARB can prevent the severe periodontitis frequently seen in Marfan syndrome.
authors.affiliation: Division of Orthodontics, Department of Human Development & Fostering, Meikai University School of Dentistry, Saitama, Japan. n-suda@dent.meikai.ac.jp
authors.forename: Naoto
authors.initials: N
authors.lastname: Suda
authors.forename: Keiji
authors.initials: K
authors.lastname: Moriyama
authors.forename: Ganjargal
authors.initials: G
authors.lastname: Ganburged
mesh_terms: D016301:Alveolar Bone Loss / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D016866:Bacteroidaceae Infections / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D001562:Benzimidazoles / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D001862:Bone Resorption / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D008382:Marfan Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010518:Periodontitis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000378:metabolism; D000077333:Telmisartan; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001565:Benzoates; D020381:Interleukin-17; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000077333:Telmisartan