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Regulation of matrix metalloproteinase-1 by Filifactor alocis in human gingival and monocytic cells

  • Marjan Nokhbehsaim
  • Andressa V. B. NogueiraEmail author
  • Anna Damanaki
  • Georgia Dalagiorgou
  • Sigrun Eick
  • Christos Adamopoulos
  • Christina Piperi
  • Efthimia K. Basdra
  • Athanasios G. Papavassiliou
  • James Deschner
Original Article

Abstract

Objectives

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.

Results

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.

Conclusions

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.

Clinical relevance

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.

Keywords

Periodontitis Filifactor alocis MMP-1 Gingival fibroblast Monocytes 

Notes

Acknowledgments

The authors would like to thank Prof. Werner Götz, Ms. Ramona Menden, and Ms. Silke van Dyck for their valuable support.

Authors’ contributions

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.

Funding

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

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, Flemmig TF, Garcia R, Giannobile WV, Graziani F, Greenwell H, Herrera D, Kao RT, Kebschull M, Kinane DF, Kirkwood KL, Kocher T, Kornman KS, Kumar PS, Loos BG, Machtei E, Meng H, Mombelli A, Needleman I, Offenbacher S, Seymour GJ, Teles R, Tonetti MS (2018) Periodontitis: consensus report of workgroup 2 of the 2017 world workshop on the classification of periodontal and peri-implant diseases and conditions. J Periodontol 89:S173–S182.  https://doi.org/10.1002/JPER.17-0721 CrossRefPubMedGoogle Scholar
  2. 2.
    Carvalho-Filho PC, Gomes-Filho IS, Meyer R, Olczak T, Xavier MT, Trindade SC (2016) Role of Porphyromonas gingivalis HmuY in immunopathogenesis of chronic periodontitis. Mediat Inflamm 2016:7465852.  https://doi.org/10.1155/2016/7465852 CrossRefGoogle Scholar
  3. 3.
    Silva N, Abusleme L, Bravo D, Dutzan N, Garcia-Sesnich J, Vernal R, Hernández M, Gamonal J (2015) Host response mechanisms in periodontal diseases. J Appl Oral Sci 23:329–355.  https://doi.org/10.1590/1678-775720140259 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Hajishengallis G, Lamont RJ (2012) Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology. Mol Oral Microbiol 27:409–419.  https://doi.org/10.1111/j.2041-1014.2012.00663.x CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Aruni AW, Roy F, Fletcher HM (2011) Filifactor alocis has virulence attributes that can enhance its persistence under oxidative stress conditions and mediate invasion of epithelial cells by Porphyromonas gingivalis. Infect Immun 79:3872–3886.  https://doi.org/10.1128/IAI.05631-11 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Schlafer S, Riep B, Griffen AL, Petrich A, Hübner J, Berning M, Friedmann A, Göbel UB, Moter A (2010) Filifactor alocis--involvement in periodontal biofilms. BMC Microbiol 10:66.  https://doi.org/10.1186/1471-2180-10-66 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Vieira Colombo AP, Magalhães CB, Hartenbach FA, Martins do Souto R, Maciel d, SilvaBoghossian C (2016) Periodontal-disease-associated biofilm: a reservoir for pathogens of medical importance. Microb Pathog 94:27–34.  https://doi.org/10.1016/j.micpath.2015.09.009 CrossRefPubMedGoogle Scholar
  8. 8.
    Oliveira RR, Fermiano D, Feres M, Figueiredo LC, Teles FR, Soares GM, Faveri M (2016) Levels of candidate periodontal pathogens in subgingival biofilm. J Dent Res 95:711–718.  https://doi.org/10.1177/0022034516634619 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Chen H, Liu Y, Zhang M, Wang G, Qi Z, Bridgewater L, Zhao L, Tang Z, Pang X (2015) A Filifactor alocis-centered co-occurrence group associates with periodontitis across different oral habitats. Sci Rep 5(9053).  https://doi.org/10.1038/srep09053
  10. 10.
    Wang Q, Jotwani R, Le J, Krauss JL, Potempa J, Coventry SC, Uriarte SM, Lamont RJ (2014) Filifactor alocis infection and inflammatory responses in the mouse subcutaneous chamber model. Infect Immun 82:1205–1212.  https://doi.org/10.1128/IAI.01434-13 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Moffatt CE, Whitmore SE, Griffen AL, Leys EJ, Lamont RJ (2011) Filifactor alocis interactions with gingival epithelial cells. Mol Oral Microbiol 26:365–373.  https://doi.org/10.1111/j.2041-1014.2011.00624.x CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Aruni AW, Roy F, Sandberg L, Fletcher HM (2012) Proteome variation among Filifactor alocis strains. Proteomics 12:3343–3364.  https://doi.org/10.1002/pmic.201200211 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Sorsa T, Tjäderhane L, Konttinen YT, Lauhio A, Salo T, Lee HM, Golub LM, Brown DL, Mäntylä P (2006) Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation. Ann Med 38:306–321.  https://doi.org/10.1080/07853890600800103 CrossRefPubMedGoogle Scholar
  14. 14.
    Hannas AR, Pereira JC, Granjeiro JM, Tjäderhane L (2007) The role of matrix metalloproteinases in the oral environment. Acta Odontol Scand 65:1–13.  https://doi.org/10.1080/00016350600963640 CrossRefPubMedGoogle Scholar
  15. 15.
    Wang J, Yang D, Li C, Shang S, Xiang J (2014) Expression of extracellular matrix metalloproteinase inducer glycosylation and caveolin-1 in healthy and inflamed human gingiva. J Periodontal Res 49:197–204.  https://doi.org/10.1111/jre.12095 CrossRefPubMedGoogle Scholar
  16. 16.
    Popat PR, Bhavsar NV, Popat PR (2014) Gingival crevicular fluid levels of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in periodontal health and disease. Singap Dent J 35:59–64.  https://doi.org/10.1016/j.sdj.2014.07.003 CrossRefGoogle Scholar
  17. 17.
    Alfant B, Shaddox LM, Tobler J, Magnusson I, Aukhil I, Walker C (2008) Matrix metalloproteinase levels in children with aggressive periodontitis. J Periodontol 79:819–826.  https://doi.org/10.1902/jop.2008.070513 CrossRefPubMedGoogle Scholar
  18. 18.
    Ghodpage PS, Kolte RA, Kolte AP, Gupta M (2014) Influence of phase I periodontal therapy on levels of matrix metalloproteinase 1 and tissue inhibitor of metalloproteinase 1. Saudi Dent J (The Saudi Dental Journal) 26:171–175.  https://doi.org/10.1016/j.sdentj.2014.05.003 CrossRefGoogle Scholar
  19. 19.
    Tüter G, Kurtiş B, Serdar M (2002) Effects of phase I periodontal treatment on gingival crevicular fluid levels of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase1. J Periodontol 73:487–493.  https://doi.org/10.1902/jop.2002.73.5.487 CrossRefPubMedGoogle Scholar
  20. 20.
    Damanaki A, Nokhbehsaim M, Eick S, Götz W, Winter J, Wahl G, Jäger A, Jepsen S, Deschner J (2014) Regulation of NAMPT in human gingival fibroblasts and biopsies. Mediat Inflamm 2014:912821.  https://doi.org/10.1155/2014/912821 CrossRefGoogle Scholar
  21. 21.
    Siqueira JF, Rôças IN (2004) Simultaneous detection of Dialister pneumosintes and Filifactor alocis in endodontic infections by 16S rDNA-directed multiplex PCR. J Endod 30:851–854CrossRefPubMedGoogle Scholar
  22. 22.
    Aruni AW, Mishra A, Dou Y, Chioma O, Hamilton BN, Fletcher HM (2015) Filifactor alocis-a new emerging periodontal pathogen. Microbes Infect 17:517–530.  https://doi.org/10.1016/j.micinf.2015.03.011 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Sorsa T, Tjäderhane L, Salo T (2004) Matrix metalloproteinase (MMPs) in oral diseases. Oral Dis 10:311–318.  https://doi.org/10.1111/j.1601-0825.2004.01038.x CrossRefPubMedGoogle Scholar
  24. 24.
    McQuibban GA, Gong JH, Wong JP, Wallace JL, Clark-Lewis I, Overall CM (2002) Matrix metalloproteinase processing of monocyte chemoattractant proteins generates CC chemokine receptor antagonists with anti-inflammatory properties in vivo. Blood 100:1160–1167CrossRefPubMedGoogle Scholar
  25. 25.
    Chioma O, Aruni AW, Milford TA, Fletcher HM (2017) Filifactor alocis collagenase can modulate apoptosis of normal oral keratinocytes. Mol Oral Microbiol 32:166–177.  https://doi.org/10.1111/omi.12163 CrossRefPubMedGoogle Scholar
  26. 26.
    Armstrong CL, Miralda I, Neff AC, Tian S, Vashishta A, Perez L, Le J, Lamont RJ, Uriarte SM (2016) Filifactor alocis promotes neutrophil degranulation and chemotactic activity. Infect Immun 84:3423–3433.  https://doi.org/10.1128/IAI.00496-16 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Marjan Nokhbehsaim
    • 1
  • Andressa V. B. Nogueira
    • 2
    Email author
  • Anna Damanaki
    • 2
  • Georgia Dalagiorgou
    • 3
  • Sigrun Eick
    • 4
  • Christos Adamopoulos
    • 3
  • Christina Piperi
    • 3
  • Efthimia K. Basdra
    • 3
  • Athanasios G. Papavassiliou
    • 3
  • James Deschner
    • 2
  1. 1.Section of Experimental Dento-Maxillo-Facial Medicine, Center of Dento-Maxillo-Facial MedicineUniversity of BonnBonnGermany
  2. 2.Department of Periodontology and Operative DentistryUniversity Medical Center of the Johannes Gutenberg UniversityMainzGermany
  3. 3.Department of Biological Chemistry, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
  4. 4.Department of Periodontology, Laboratory of Oral MicrobiologyUniversity of BernBernSwitzerland

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