Activation and novel processing of matrix metalloproteinases by a thiol-proteinase from the oral anaerobe Porphyromonas gingivalis

A. A. DeCarlo, L. Windsor, M. K. Bodden, G. J. Harber, B. Birkedal-Hansen, H. Birkedal-Hansen

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

A critical outcome of periodontal disease is degradation of the collagenous periodontal ligament that connects teeth to bone in the dental arch. Periodontal diseases occur in response to bacterial colonization of the teeth, but their molecular pathogenesis is still speculative. One family of enzymes, known as the matrix metalloproteinases (MMPs), has been implicated in the degradation of the periodontal ligament. MMPs, which are also suspected to play a role in many other physiologic and pathologic remodeling processes, can be secreted by epithelial cells surrounding the teeth and are found in relative abundance in tissues and fluids near periodontally diseased sites. Since most MMPs are secreted as inactive zymogens which may be activated by limited proteolysis, it has been suggested that proteinases expressed by the infecting periodontal pathogens might activate latent host MMPs to initiate or accelerate degradation of the collagenous periodontal ligament. The aim of this work was to examine interactions between purified host MMPs and bacterial proteinase. In this article, we demonstrate that a proteinase isolated from the periodontopathogen Porphyromonas gingivalis can activate MMP-1, MMP-3, and MMP-9 and can catalyze the superactivation of MMP-1 by MMP-3. Activation of these MMPs is demonstrated to result from initital hydrolysis within their propeptide. Also, for MMP-1 and MMP-9, the P. gingivalis proteinase cleaves the MMP propeptide following a lysine residue at a previously unreported site which, for both MMPs, is one residue NH2-terminal to the known autocatalytic cleavage site. These data describe a mode of virulence for the periodontopathogen Porphyromonas gingivalis that involves activation of host-degradative enzymes.

Original languageEnglish (US)
Pages (from-to)1260-1270
Number of pages11
JournalJournal of Dental Research
Volume76
Issue number6
StatePublished - Jun 1997
Externally publishedYes

Fingerprint

Porphyromonas gingivalis
Matrix Metalloproteinases
Sulfhydryl Compounds
Peptide Hydrolases
Periodontal Ligament
Matrix Metalloproteinase 1
Matrix Metalloproteinase 3
Tooth
Matrix Metalloproteinase 9
Periodontal Diseases
Secreted Matrix Metalloproteinases
Dental Arch
Enzyme Precursors
Pathologic Processes
Enzymes
Proteolysis
Lysine
Virulence
Hydrolysis
Epithelial Cells

Keywords

  • Amino acid sequencing
  • Cysteine proteinases
  • Metalloproteinases
  • Porphyromonas gingivalis
  • Western blotting

ASJC Scopus subject areas

  • Dentistry(all)

Cite this

DeCarlo, A. A., Windsor, L., Bodden, M. K., Harber, G. J., Birkedal-Hansen, B., & Birkedal-Hansen, H. (1997). Activation and novel processing of matrix metalloproteinases by a thiol-proteinase from the oral anaerobe Porphyromonas gingivalis. Journal of Dental Research, 76(6), 1260-1270.

Activation and novel processing of matrix metalloproteinases by a thiol-proteinase from the oral anaerobe Porphyromonas gingivalis. / DeCarlo, A. A.; Windsor, L.; Bodden, M. K.; Harber, G. J.; Birkedal-Hansen, B.; Birkedal-Hansen, H.

In: Journal of Dental Research, Vol. 76, No. 6, 06.1997, p. 1260-1270.

Research output: Contribution to journalArticle

DeCarlo, AA, Windsor, L, Bodden, MK, Harber, GJ, Birkedal-Hansen, B & Birkedal-Hansen, H 1997, 'Activation and novel processing of matrix metalloproteinases by a thiol-proteinase from the oral anaerobe Porphyromonas gingivalis', Journal of Dental Research, vol. 76, no. 6, pp. 1260-1270.
DeCarlo, A. A. ; Windsor, L. ; Bodden, M. K. ; Harber, G. J. ; Birkedal-Hansen, B. ; Birkedal-Hansen, H. / Activation and novel processing of matrix metalloproteinases by a thiol-proteinase from the oral anaerobe Porphyromonas gingivalis. In: Journal of Dental Research. 1997 ; Vol. 76, No. 6. pp. 1260-1270.
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AU - DeCarlo, A. A.

AU - Windsor, L.

AU - Bodden, M. K.

AU - Harber, G. J.

AU - Birkedal-Hansen, B.

AU - Birkedal-Hansen, H.

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N2 - A critical outcome of periodontal disease is degradation of the collagenous periodontal ligament that connects teeth to bone in the dental arch. Periodontal diseases occur in response to bacterial colonization of the teeth, but their molecular pathogenesis is still speculative. One family of enzymes, known as the matrix metalloproteinases (MMPs), has been implicated in the degradation of the periodontal ligament. MMPs, which are also suspected to play a role in many other physiologic and pathologic remodeling processes, can be secreted by epithelial cells surrounding the teeth and are found in relative abundance in tissues and fluids near periodontally diseased sites. Since most MMPs are secreted as inactive zymogens which may be activated by limited proteolysis, it has been suggested that proteinases expressed by the infecting periodontal pathogens might activate latent host MMPs to initiate or accelerate degradation of the collagenous periodontal ligament. The aim of this work was to examine interactions between purified host MMPs and bacterial proteinase. In this article, we demonstrate that a proteinase isolated from the periodontopathogen Porphyromonas gingivalis can activate MMP-1, MMP-3, and MMP-9 and can catalyze the superactivation of MMP-1 by MMP-3. Activation of these MMPs is demonstrated to result from initital hydrolysis within their propeptide. Also, for MMP-1 and MMP-9, the P. gingivalis proteinase cleaves the MMP propeptide following a lysine residue at a previously unreported site which, for both MMPs, is one residue NH2-terminal to the known autocatalytic cleavage site. These data describe a mode of virulence for the periodontopathogen Porphyromonas gingivalis that involves activation of host-degradative enzymes.

AB - A critical outcome of periodontal disease is degradation of the collagenous periodontal ligament that connects teeth to bone in the dental arch. Periodontal diseases occur in response to bacterial colonization of the teeth, but their molecular pathogenesis is still speculative. One family of enzymes, known as the matrix metalloproteinases (MMPs), has been implicated in the degradation of the periodontal ligament. MMPs, which are also suspected to play a role in many other physiologic and pathologic remodeling processes, can be secreted by epithelial cells surrounding the teeth and are found in relative abundance in tissues and fluids near periodontally diseased sites. Since most MMPs are secreted as inactive zymogens which may be activated by limited proteolysis, it has been suggested that proteinases expressed by the infecting periodontal pathogens might activate latent host MMPs to initiate or accelerate degradation of the collagenous periodontal ligament. The aim of this work was to examine interactions between purified host MMPs and bacterial proteinase. In this article, we demonstrate that a proteinase isolated from the periodontopathogen Porphyromonas gingivalis can activate MMP-1, MMP-3, and MMP-9 and can catalyze the superactivation of MMP-1 by MMP-3. Activation of these MMPs is demonstrated to result from initital hydrolysis within their propeptide. Also, for MMP-1 and MMP-9, the P. gingivalis proteinase cleaves the MMP propeptide following a lysine residue at a previously unreported site which, for both MMPs, is one residue NH2-terminal to the known autocatalytic cleavage site. These data describe a mode of virulence for the periodontopathogen Porphyromonas gingivalis that involves activation of host-degradative enzymes.

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