Montero-Melendez Trinidad, Madeira Mila F M, Norling Lucy V, Alsam Asil, Curtis Michael A, da Silva Tarcília A, Perretti Mauro
The William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Department of Oral Pathology, Faculty of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Am J Pathol. 2014 Aug;184(8):2333-41. doi: 10.1016/j.ajpath.2014.04.009. Epub 2014 Jun 27.
Because there is clinical evidence for an association between periodontal disease and rheumatoid arthritis, it is important to develop suitable experimental models to explore pathogenic mechanisms and therapeutic opportunities. The K/BxN serum model of inflammatory arthritis was applied using distinct protocols, and modulation of joint disruption afforded by dexamethasone and calcitonin was established in comparison to the melanocortin (MC) receptor agonist DTrp(8)-γ-melanocyte stimulating hormone (MSH; DTrp). Wild-type and MC receptor type 3 (MC3)-null mice of different ages were also used. There was significant association between severity of joint disease, induced with distinct protocols and volumes of the arthritogenic K/BxN serum, and periodontal bone damage. Therapeutic treatment with 10 μg dexamethasone, 30 ng elcatonin, and 20 μg DTrp per mouse revealed unique and distinctive pharmacological properties, with only DTrp protecting both joint and periodontal tissue. Further analyses in nonarthritic animals revealed higher susceptibility to periodontal bone loss in Mc3r(-/-) compared with wild-type mice, with significant exacerbation at 14 weeks of age. These data reveal novel protective properties of endogenous MC3 on periodontal status in health and disease and indicate that MC3 activation could lead to the development of a new genus of anti-arthritic bone-sparing therapeutics.
由于有临床证据表明牙周病与类风湿性关节炎之间存在关联，因此开发合适的实验模型以探索致病机制和治疗机会很重要。使用不同方案应用炎性关节炎的K/BxN血清模型，并与促黑素（MC）受体激动剂DTrp(8)-γ-黑素细胞刺激素（MSH；DTrp）比较，确定地塞米松和降钙素对关节破坏的调节作用。还使用了不同年龄的野生型和3型MC受体（MC3）基因敲除小鼠。用不同方案和不同体积的致关节炎K/BxN血清诱导的关节疾病严重程度与牙周骨损伤之间存在显著关联。每只小鼠用10μg地塞米松﹑30ng依降钙素和20μg DTrp进行治疗显示出独特的药理学特性，只有DTrp对关节和牙周组织均有保护作用。对非关节炎动物的进一步分析显示，与野生型小鼠相比，Mc3r(-/-)小鼠对牙周骨丢失更易感，在14周龄时显著加重。这些数据揭示了内源性MC3在健康和疾病状态下对牙周状况的新保护特性，并表明激活MC3可能会导致开发出一类新型的抗关节炎保骨疗法。
