title: Association between periodontal disease and inflammatory arthritis reveals modulatory functions by melanocortin receptor type 3.
abstract: 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.
authors: The William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors: Trinidad
authors: T
authors: Montero-Melendez
authors: Department of Oral Pathology, Faculty of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Mila F M
authors: MF
authors: Madeira
authors: The William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors: Lucy V
authors: LV
authors: Norling
authors: Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors: Asil
authors: A
authors: Alsam
authors: Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors: Michael A
authors: MA
authors: Curtis
authors: Department of Oral Pathology, Faculty of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Tarcília A
authors: TA
authors: da Silva
authors: The William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom. Electronic address: m.perretti@qmul.ac.uk.
authors: Mauro
authors: M
authors: Perretti
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000150:complications / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010510:Periodontal Diseases / Q000150:complications / Q000378:metabolism*; D044104:Receptor, Melanocortin, Type 3 / Q000378:metabolism*
chemical_list: D044104:Receptor, Melanocortin, Type 3