Induction of matrix metalloproteinases and a collagen-degrading phenotype in fibroblasts and epithelial cells by secreted Porphyromonas gingivalis proteinase

J Periodontal Res. 1998 Oct;33(7):408-20. doi: 10.1111/j.1600-0765.1998.tb02337.x.


Periodontitis is characterized by advancement of a narrow band of epithelium (1-10 cells wide) through the collagenous periodontal ligament in response to bacterial accumulation and infection. A modulating role by epithelial cells in the progression of periodontitis was hypothesized due to the close proximity of the advancing epithelium to both the etiological bacteria and to the collagen fibers of the ligament. We demonstrate that rat mucosal epithelial cells and human fibroblasts are similarly stimulated to degrade a collagen type I cellular substrate by thiol-dependent activity released by the major periodontal pathogen Porphyromonas gingivalis. A purified, extracellular bacterial thiol-proteinase from P. gingivalis ATCC 33277 stimulated mucosal epithelial cells to upregulate expression of collagenase and stromelysin, and to degrade a collagen type I fibril matrix. Stimulation of the epithelial cells with this purified proteinase was associated with morphological changes in the cells and with accumulation of secreted latent procollagenase throughout the culture medium. Release of active collagenase was minimal and collagen degradation by the epithelial cells was discreet and localized subcellularly suggesting the possibility that activation of secreted procollagenase was cell-associated. We conclude that a collagen-degrading phenotype can be stimulated in relatively quiescent mucosal epithelial cells and fibroblasts by the presence of bacterial proteinase. These experiments suggest roles for the P. gingivalis thiol-proteinase and the epithelial cell in the pathogenesis of periodontal disease and demonstrate the potential for dysregulation of extracellular matrix remodeling events during healing of other bacterially infected wounds.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adhesins, Bacterial
  • Animals
  • Bacterial Proteins / metabolism
  • Base Sequence
  • Cells, Cultured
  • Collagen / metabolism
  • Culture Media, Conditioned
  • Cysteine Endopeptidases / metabolism*
  • Epithelial Cells / metabolism
  • Extracellular Matrix / metabolism
  • Fibroblasts / metabolism
  • Gingipain Cysteine Endopeptidases
  • Hemagglutinins / metabolism
  • Humans
  • Metalloendopeptidases / biosynthesis*
  • Molecular Sequence Data
  • Mouth Mucosa / metabolism
  • Periodontal Ligament / cytology
  • Periodontal Ligament / metabolism*
  • Periodontitis / enzymology*
  • Periodontitis / microbiology
  • Porphyromonas gingivalis / enzymology*
  • Porphyromonas gingivalis / pathogenicity
  • RNA, Messenger / analysis
  • Rats
  • Up-Regulation


  • Adhesins, Bacterial
  • Bacterial Proteins
  • Culture Media, Conditioned
  • Gingipain Cysteine Endopeptidases
  • Hemagglutinins
  • RNA, Messenger
  • Collagen
  • Cysteine Endopeptidases
  • Metalloendopeptidases

Associated data

  • GENBANK/M19533
  • GENBANK/M60616
  • GENBANK/X02601