MIF induces osteoclast differentiation and contributes to progression of periodontal disease in mice.
Periodontal disease (PD) is a chronic inflammatory and alveolar bone destructive disease triggered by microorganisms from the oral biofilm. Oral inoculation of mice with the periodontopathogen Aggregatibacter actinomycetemcomitans (Aa) induces marked alveolar bone loss and local production of inflammatory mediators, including Macrophage Migration Inhibitory Factor (MIF). The role of MIF for alveolar bone resorption during PD is not known. In the present study, experimental PD was induced in BALB/c wild-type mice (WT) and MIF knockout mice (MIF⁻/⁻) through oral inoculation of Aa. Despite enhanced number of bacteria, MIF⁻/⁻ mice had reduced infiltration of TRAP-positive cells and reduced alveolar bone loss. This was associated with decreased neutrophil accumulation and increased levels of IL-10 in periodontal tissues. TNF-α production was similar in both groups. In vitro, LPS from Aa enhanced osteoclastic activity in a MIF-dependent manner. In conclusion, MIF has role in controlling bacterial growth in the context of PD but contributes more significantly to the progression of bone loss during PD by directly affecting differentiation and activity of osteoclasts.
Department of Microbiology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Mila Fernandes Moreira
MF
Madeira
Celso Martins
CM
Queiroz-Junior
Graciela Mitre
GM
Costa
Patrícia Campi
PC
Santos
Elcia Maria
EM
Silveira
Gustavo Pompermaier
GP
Garlet
Patrícia Silva
PS
Cisalpino
Mauro Martins
MM
Teixeira
Tarcília Aparecida
TA
Silva
Daniele da Glória
Dda G
Souza
D016301:Alveolar Bone Loss / Q000382:microbiology / Q000473:pathology*; D000818:Animals; D002454:Cell Differentiation; D004195:Disease Models, Animal; D018450:Disease Progression; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D015661:Pasteurellaceae / Q000254:growth & development / Q000502:physiology*; D016871:Pasteurellaceae Infections / Q000382:microbiology / Q000473:pathology*; D010510:Periodontal Diseases / Q000382:microbiology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018836:Inflammation Mediators; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse