Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in Auditorium 1 of the Institute of Dentistry, on December 10th, 2004, at 12 noon.
The dentin-pulp complex comprises mineralized dentin and the vital soft tissues encased inside dentin, i.e. odontoblasts and pulp tissue. During caries progression, the dentinal minerals are dissolved and eventually the collagenous organic matrix is degraded. However, the exact mechanisms and enzymes responsible for the organic matrix breakdown remain unknown. Matrix metalloproteinases (MMPs), a family of endopeptidases capable of degrading in concert virtually all extracellular matrix components, are expressed during normal dentin-pulp complex formation and maintenance. MMP activity has also been suggested to contribute to the organic matrix degradation during dentin caries progression and to the repair and defense reactions elicited by caries in the dentin-pulp complex cells. The aim of the study was to further elucidate the role of host MMPs in dentin caries progression and the origin of MMPs in carious dentin as well as the possible changes in MMP expression in the cells of the dentin-pulp complex in response to caries.
MMP inhibitors decreased the area of dentin caries lesions in vivo, suggesting the involvement of host MMPs in dentin caries pathogenesis. When the overall MMP gene expression was examined by cDNA microarray, pooled pulp samples demonstrated a high level of MMP-13 expression, but failed to show any unequivocal changes in MMP expression due to caries. MMP-13 expression is rare among normal human adult tissues. Real-time quantitative PCR of individual pulp and odontoblast samples demonstrated a rather large variation in relative MMP-13 mRNA expression between samples, especially pulp samples. Protein expression of MMP-13 was detected in pulp and odontoblasts without any major differences between the tissues of sound and carious teeth. This was also the case with the MMP-20 (enamelysin) protein, which was demonstrated in odontoblasts and the pulp tissue of fully developed human teeth. MMP-20, MMP-8, and gelatinases (especially MMP-2) were demonstrated in human dentin, and dentinal MMPs exhibited activity against native and denatured type I collagen when released.
The study demonstrates the presence of MMPs in the soft and hard tissue compartments of the dentin-pulp complex. These enzymes may also contribute to dentin caries progression and response reactions to caries.