title: Melanocortin agonism as a viable strategy to control alveolar bone loss induced by oral infection.
abstract: Alveolar bone loss is a result of an aggressive form of periodontal disease (PD) associated with Aggregatibacter actinomycetemcomitans (Aa) infection. PD is often observed with other systemic inflammatory conditions, including arthritis. Melanocortin peptides activate specific receptors to exert antiarthritic properties, avoiding excessing inflammation and modulating macrophage function. Recent work has indicated that melanocortin can control osteoclast development and function, but whether such protection takes place in infection-induced alveolar bone loss has not been investigated. The purpose of this study was to evaluate the role of melanocortin in Aa-induced PD. Mice were orally infected with Aa and treated with the melanocortin analog DTrp8-γMSH or vehicle daily for 30 d. Then, periodontal tissue was collected and analyzed. Aa-infected mice treated with DTrp8-γMSH presented decreased alveolar bone loss and a lower degree of neutrophil infiltration in the periodontium than vehicle-treated animals; these actions were associated with reduced periodontal levels of TNF-α, IFN-γ, and IL-17A. In vitro experiments with cells differentiated into osteoclasts showed that osteoclast formation and resorptive activity were attenuated after treatment with DTrp8-γMSH. Thus, melanocortin agonism could represent an innovative way to tame overexuberant inflammation and, at the same time, preserve bone physiology, as seen after Aa infection.-Madeira, M. F. M., Queiroz-Junior, C. M., Montero-Melendez, T., Werneck, S. M. C., Corrêa, J. D., Soriani, F. M., Garlet, G. P., Souza, D. G., Teixeira, M. M., Silva, T. A., Perretti, M. Melanocortin agonism as a viable strategy to control alveolar bone loss induced by oral infection.
authors.affiliation: Department of Microbiology, Biologic Science Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; madeiramila@gmail.com.|Department of Oral Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Mila F M
authors.initials: MF
authors.lastname: Madeira
authors.affiliation: Department of Morphology, Biologic Science Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Celso M
authors.initials: CM
authors.lastname: Queiroz-Junior
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Trinidad
authors.initials: T
authors.lastname: Montero-Melendez
authors.affiliation: Department of Microbiology, Biologic Science Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Silvia M C
authors.initials: SM
authors.lastname: Werneck
authors.affiliation: Department of Oral Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Jôice D
authors.initials: JD
authors.lastname: Corrêa
authors.affiliation: Department of General Biology, Biologic Science Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Frederico M
authors.initials: FM
authors.lastname: Soriani
authors.affiliation: Department of Biological Sciences, School of Dentistry of Bauru, Universidade de São Paulo, Bauru, São Paulo, Brazil; and.
authors.forename: Gustavo P
authors.initials: GP
authors.lastname: Garlet
authors.affiliation: Department of Microbiology, Biologic Science Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Daniele G
authors.initials: DG
authors.lastname: Souza
authors.affiliation: Department of Biochemistry and Immunology, Biologic Science Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
authors.affiliation: Department of Oral Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Tarcilia A
authors.initials: TA
authors.lastname: Silva
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans; D016301:Alveolar Bone Loss / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000276:immunology; D053486:Melanocortins / Q000819:agonists*; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000382:microbiology*; D016871:Pasteurellaceae Infections / Q000517:prevention & control*; D010510:Periodontal Diseases / Q000378:metabolism*; D010518:Periodontitis / Q000188:drug therapy / Q000378:metabolism
chemical_list: D053486:Melanocortins
keywords: Aggregatibacter actinomycetemcomitans; DTrp8-γMSH; inflammation; osteoclasts; periodontitis