Stimulation of Matrix Metalloproteinases by Black-Pigmented Bacteroides in Human Pulp and Periodontal Ligament Cell Cultures

Abstract

Matrix metalloproteinases (MMPs) are a group of proteolytic enzymes capable of degrading most components of the extracellular matrix. Recently, evidence has shown that MMPs may play a role in tissue degradation in inflamed dental pulp. To date very little is known regarding the mechanism of extracellular matrix destruction at the site of bacterial infection. The purpose of this study was to determine the effects of the supernatants from Porphyromonas endodontalis and Porphyromonas gingivalis on the production and secretion of MMPs by primary human pulp and periodontal ligament (PDL) cell cultures in vitro. The results were evaluated by substrate gel zymography from long-term cultures. The main gelatinase secreted by human pulp and PDL cells migrated at 72 kDa and represented MMP-2. Minor gelatinolytic bands were also observed at 92 kDa regions that correspond to MMP-9. After an 8-day culture period, P. endodontalis and P. gingivalis were found to elevate MMP-2 production both in human pulp and PDL cell cultures. In addition, the stimulation was in a dose- and time-dependent manner. Both human pulp and PDL cells, however, treated with either P. endodontalis or P. gingivalis had no effect on the pattern of MMP-9 produced or secreted in either cell extracts or conditioned medium fractions. These results indicate that black-pigmented Bacteroides species play an important role in tissue destruction and disintegration of extracellular matrix in pulpal and periapical diseases. Thus, activation of MMPs may be one of the distinct host degradative pathways in the pathogenesis of microbial-induced pulpal and periapical lesion. An understanding of the actions of these black-pigmented Bacteroides species on pulp and PDL cells may result in new therapies to augment current treatment of pulpal and periapical lesions.

MMP2 and MMP9 are Associated with Apical Periodontitis Progression and Might be Modulated by TLR2 and MyD88

“…Bacterial infection is a condition for the development of periapical lesions when it is derived from extensive carious lesions. MMP9 production was enhanced in human pulp and periodontal ligament cells stimulated with endodontic pathogens (23).…”

“…MMP2 modulates many physiological conditions including wound repair and tissue remodeling (22). In physiological condition, MMP2 is expressed by periodontal ligament cells (23) and acts in response to infection, tissue remodeling and injury. In our study, we observed that MMP2 expression was lower in the TLR2 KO mice than in the WT at 42 days.…”

MMP-1 and TIMP-1 production in MG-63 cells stimulated withPrevotella nigrescenslipopolysaccharide

“…There are increasing evidences that MMPs are essential enzymes responsible for degradation of extracellular matrix in the pathological condi- 19) . Numerous studies have examined MMPs secreted from periodontal ligament fibroblast [20][21][22] and correlated the level of expression with the invasive ability of the disease 4,6) . Individual osteoblasts, like fibroblasts, are capable of both synthesizing and degrading their respective organic matrices in vivo 23) .…”

“…It is con-ABSTRACT ceivable that, since the major component of the organic bone matrix is collagen, collagenolytic enzyme, synthesized by osteoblasts, may also participate in the degradation of the mineralized collagen during bone resorption 3) . Matrix metalloproteinases (MMPs) are well known proteolytic enzymes for the degradation of extracellular matrix and this proteolysis is believed to play an essential role in the development and progression of pulpal and periapical inflammation 4) . MMPs, produced by osteoblastlike cells, are likely to be involved in various steps of the bone resorption process 5) .…”

“…Recently, it was demonstrated that black-pigmented Bacteroides (BPB) species play an important role in tissue disintegration of extracellular matrix in pulpal and periapical diseases 4,11) . The cells of these lesions respond to LPS of the organisms and produce various inflammatory mediators.…”