Queiroz-Junior C M, Silveira K D, de Oliveira C R, Moura A P, Madeira M F M, Soriani F M, Ferreira A J, Fukada S Y, Teixeira M M, Souza D G, da Silva T A
Department of Oral Surgery and Pathology, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
J Periodontal Res. 2015 Dec;50(6):814-23. doi: 10.1111/jre.12269. Epub 2015 Mar 5.
The angiotensin type 1 (AT1) receptor has been implicated in the pathogenesis of inflammatory bone disorders. This study aimed to investigate the effect of an AT1 receptor antagonist in infection-induced and arthritis-associated alveolar bone loss in mice.
Mice were subjected to Aggregatibacter actinomycetemcomitans oral infection or antigen-induced arthritis and treated daily with 10 mg/kg of the prototype AT1 antagonist, losartan. Treatment was conducted for 30 d in the infectious condition and for 17 d and 11 d in the preventive or therapeutic regimens in the arthritic model, respectively. The mice were then killed, and the maxillae, serum and knee joints were collected for histomorphometric and immunoenzymatic assays. In vitro osteoclast assays were performed using RAW 264.7 cells stimulated with A. actinomycetemcomitans lipopolysacharide (LPS).
Arthritis and A. actinomycetemcomitans infection triggered significant alveolar bone loss in mice and increased the levels of myeloperoxidase and of TRAP(+) osteoclasts in periodontal tissues. Losartan abolished such a phenotype, as well as the arthritis joint inflammation. Both arthritis and A. actinomycetemcomitans conditions were associated with the release of tumor necrosis factor alpha (TNF-α), interferon-gamma, interleukin-17 and chemokine (C-X-C motif) ligand 1 and an increased RANKL/osteoprotegerin ratio in periodontal tissues, but such expression decreased after losartan treatment, except for TNF-α. The therapeutic approach was as beneficial as the preventive one. In vitro, losartan prevented LPS-induced osteoclast differentiation and activity.
The blockade of AT1 receptor exerts anti-inflammatory and anti-osteoclastic effects, thus protecting periodontal tissues in distinct pathophysiological conditions of alveolar bone loss.
血管紧张素1型（AT1）受体与炎性骨疾病的发病机制有关。本研究旨在探讨AT1受体拮抗剂对小鼠感染诱导型和关节炎相关型牙槽骨丧失的影响。
将小鼠进行伴放线聚集杆菌口腔感染或抗原诱导性关节炎造模，每天用10mg/kg的原型AT1拮抗剂氯沙坦进行治疗。在感染情况下治疗30天，在关节炎模型的预防或治疗方案中分别治疗17天和11天。然后处死小鼠，收集上颌骨、血清和膝关节进行组织形态计量学和免疫酶分析。使用伴放线聚集杆菌脂多糖（LPS）刺激的RAW 264.7细胞进行体外破骨细胞分析。
关节炎和伴放线聚集杆菌感染引发小鼠显著的牙槽骨丧失，并增加牙周组织中髓过氧化物酶和TRAP(+)破骨细胞的水平。氯沙坦消除了这种表型以及关节炎关节炎症。关节炎和伴放线聚集杆菌感染均与肿瘤坏死因子α（TNF-α）、干扰素-γ、白细胞介素-17和趋化因子（C-X-C基序）配体1的释放以及牙周组织中RANKL/骨保护素比值增加有关，但氯沙坦治疗后除TNF-α外，这些表达均降低。治疗方法与预防方法一样有益。在体外，氯沙坦可防止LPS诱导的破骨细胞分化和活性。
阻断AT1受体具有抗炎和抗破骨细胞作用，从而在牙槽骨丧失的不同病理生理条件下保护牙周组织。
