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

Clin Oral Investig. 2020 Jun;24(6):1987-1995. doi: 10.1007/s00784-019-03062-0. Epub 2019 Aug 23.

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: Filifactor alocis; Gingival fibroblast; MMP-1; Monocytes; Periodontitis.

MeSH terms

  • Clostridiales* / physiology
  • Fibroblasts
  • Gingiva / metabolism
  • Humans
  • Matrix Metalloproteinase 1* / metabolism
  • Periodontitis* / metabolism
  • Periodontitis* / microbiology

Substances

  • Matrix Metalloproteinase 1

Supplementary concepts

  • Filifactor alocis