Porphyromonas gingivalis decreases osteoblast proliferation through IL-6-RANKL/OPG and MMP-9/TIMPs pathways.
BACKGROUND
Porphyromonas gingivalis, an important periodontal pathogen, is closely associated with inflammatory alveolar bone resorption. This bacterium exerts its pathogenic effect indirectly through multiple virulence factors, such as lipopolysaccharides, fimbriae, and proteases. Another possible pathogenic path may be through a direct interaction with the host's soft and hard tissues (e.g., alveolar bone), which could lead to periodontitis.


OBJECTIVE
The aim of the present study was to investigate the direct effect of live and heat-inactivated P gingivalis on bone resorption, using an in vitro osteoblast culture model.


RESULTS
Optical microscopy and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide MTT assay revealed that live P gingivalis induced osteoblast detachment and reduced their proliferation. This effect was specific to live bacteria and was dependent on their concentration. Live P gingivalis increased IL-6 mRNA expression and protein production and downregulated RANKL and OPG mRNA expression. The effect of live P gingivalis on bone resorption was strengthened by an increase in MMP-9 expression and its activity. This increase was accompanied by an increase in TIMP-1 and TIMP-2 mRNA expression and protein production by osteoblasts infected with live P gingivalis.


CONCLUSIONS
Overall, the results suggest that direct contact of P gingivalis with osteoblasts induces bone resorption through an inflammatory pathway that involves IL-6, RANKL/OPG, and MMP-9/TIMPs.
Le
Xuan Khanh
XK
Oral Ecology Research Group, Laval University, Québec City, Québec G1K 7P4, Canada.
Laflamme
Claude
C
Rouabhia
Mahmoud
M
D001862:Bone Resorption / Q000276:immunology / Q000382:microbiology; D002448:Cell Adhesion / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004396:Coloring Agents; D015536:Down-Regulation; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology*; D020778:Matrix Metalloproteinase 2 / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000276:immunology*; D010006:Osteoblasts / Q000276:immunology / Q000382:microbiology*; D053244:Osteoprotegerin / Q000276:immunology*; D016966:Porphyromonas gingivalis / Q000276:immunology*; D053245:RANK Ligand / Q000276:immunology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000276:immunology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000276:immunology; D019714:Tissue Inhibitor of Metalloproteinases / Q000276:immunology*
D004396:Coloring Agents; D015850:Interleukin-6; D053244:Osteoprotegerin; D053245:RANK Ligand; D013778:Tetrazolium Salts; D013844:Thiazoles; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C022616:thiazolyl blue