Regulation of matrix metalloproteinase-1 by Filifactor alocis in human gingival and monocytic cells
Periodontitis is a highly prevalent chronic inflammatory disease caused by periodontopathogens, such as Filifactor alocis. This study sought to examine the matrix metalloproteinase (MMP)-1 synthesis by monocytic and fibroblastic cells in response to F. alocis and to unravel the underlying cellular mechanisms.
Material and methods
Gingival biopsies from periodontally healthy and periodontitis individuals were analyzed for the presence of F. alocis and MMP-1 by RT-PCR. Human gingival fibroblastic (HGF-1) and monocytic (THP-1) cells were stimulated with F. alocis in the presence and absence of a blocking toll-like receptor (TLR)2 antibody or specific inhibitors against MAPKs. MMP-1 expression and protein levels were studied by RT-PCR and ELISA, respectively.
F. alocis was highly prevalent in biopsies from periodontitis patients but barely present in the healthy gingiva. Significantly higher MMP-1 expression levels were found in the inflamed gingiva as compared with healthy biopsies. F. alocis caused a significant and dose-dependent MMP-1 upregulation in both cells. The stimulatory effect of F. alocis on MMP-1 was TLR2- and MAPK-dependent and more pronounced on THP-1 cells as compared with HGF-1 cells.
Our results demonstrate that F. alocis and MMP-1 are more prevalent at periodontitis sites. Additionally, our study provides original evidence that F. alocis can stimulate MMP-1 production by fibroblastic and monocytic cells, suggesting that F. alocis may contribute to periodontal breakdown through MMP-1.
F. alocis and MMP-1 are linked to each other and key players in periodontitis, which may have significant implications for future diagnostic and treatment strategies.
KeywordsPeriodontitis Filifactor alocis MMP-1 Gingival fibroblast Monocytes
The authors would like to thank Prof. Werner Götz, Ms. Ramona Menden, and Ms. Silke van Dyck for their valuable support.
Defining the study aims: James Deschner; coordination of collaboration: James Deschner; planning the experiments: Marjan Nokhbehsaim, Anna Damanaki, Christina Piperi, Efthimia K. Basdra, Athanasios G. Papavassiliou, and James Deschner; growing the bacteria and preparing the bacterial lysate: Sigrun Eick; performing preexperiments: Andressa V. B. Nogueira and Anna Damanaki; performing the experiments: Marjan Nokhbehsaim, Anna Damanaki, Georgia Dalagiorgou, and Christos Adamopoulos; monitoring/supervising the experiments: Christina Piperi, Efthimia K. Basdra, Athanasios G. Papavassiliou, and James Deschner; analyzing and discussing the data: Marjan Nokhbehsaim, Andressa V. B. Nogueira, Anna Damanaki, Georgia Dalagiorgou, Christos Adamopoulos, and James Deschner; discussing the data: Sigrun Eick, Christina Piperi, Efthimia K. Basdra, and Athanasios G. Papavassiliou; creating the figures: Marjan Nokhbehsaim, Andressa V. B. Nogueira, and James Deschner; all authors contributed to the writing of the manuscript; all authors read and approved the final manuscript.
This study was supported by the Medical Faculty of the University of Bonn.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving human participants
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of the University of Bonn (043/11) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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