Dentin matrix contains matrix metalloproteinases (MMP), whose key role in the development of caries was discovered many years ago. These enzymes, though produced by the odontoblasts in the physiological conditions, are responsible for the dynamic degradation of organic structures in a demineralized dentin. It takes place by means of hydrolysis of components such as collagen fibers, or specific non-colagenous proteins. Although MMPs are synthesized in cells as inactive zymogens, and are secreted to the extracellular space in a form of harmless proenzymes, they remain very hazardous to the dentine tissue. The oral cavity pH often drops and locally remains at very low levels, especially in those anatomical structures that are hard to reach with a toothbrush. A decrease in the pH level as a result of a heavy bacterial metabolism causes destruction of hydroxyapatites in the dental hard tissue. Acidic environment has the ability to directly activate the MMPs. Once activated, enzymes break down organic components of dentine even long after the pH returns to the neutral level. The unveiling of the organic components, through the loss of inorganic compounds in the dentine (etching, tooth decay), allows MMPs to operate on a larger area, thereby increasing the dynamism of their action.
The resin that combines composite fillings and the etched tooth structure penetrates deep into the dentin tubules and between collagen fibers, forming the so-called “hybrid layer”. This layer plays a crucial role in the adhesion of composites. If the collagen fibers are damaged due to excessive etching, desiccation, or, as in this instance, metalloproteinase involving hydrolysis, filling will not have the proper adhesion. Such a filling is prone to develop microleakage and as a result it may fall out spontaneously or might require replacing – and that implicates a further loss of hard tissues.
Metalloproteinases contribute to the destruction of collagen fibers, and therefore also to the disintegration of the dentine – composite connection used in dentistry. This leads to a weakening of existing fillings, irritation of doctors and with no doubt patients’ financial strain. Can the action of MMPs in the tissues surrounding the filling be prevented? Researchers from the University of Granada (Spain) and University of Georgia (USA) have joined forces to conduct an experiment determining the effect of certain substances on the prevention of collagen degradation in hard tissues.
The experiment has been performed on human teeth – both mineralized and those treated with phosphoric acid. The compounds potentially inhibiting the degradation of collagen were: chlorhexidine digluconate, doxycycline and zinc chloride. Metalloproteinases identical to those occurring naturally in the human body were added to the half of the samples. All the specimens have been evaluated for the enzymatic destruction of collagen fibers after 24 hours, 7 and 21 days. Doxycycline, as expected, completely inhibited the proteolysis of dentin. Its chronic use in order to reduce the degradation of organic matter of the dentine, however, is inadvisable. Like any other antibiotic, it carries the risk of gastro-intestinal disorders, the emergence of antibiotic resistance, developing candidiasis or hypersensitivity reactions. Chlorhexidine digluconate decreased collagen degradation for 24 hours. Nevertheless, with prolonged use of chlorhexidine, staining of both the teeth and fillings may occur. Meanwhile inhibitory effect of excess amounts of zinc was maintained up to 3 weeks. Zinc is a relatively safe substance that can be potentially used in topical application. Its probable mechanism of action is by bonding with collagen fibers in areas particularly vulnerable to the action of metalloproteinases.
In the near future, adding zinc to composite materials should find broad recognition among scientists. Perhaps a chance to create a new formula of bonds / primers, that would include zinc in order to protect from the effects of MMPs, is at hand. Time will tell whether we are just on the threshold of a breakthrough in restorative dentistry.
Zinc reduces collagen degradation in human demineralized Dentin explants Journal of Dentistry Volume 39, Issue 2, February, 2011, pp. 148-153 Osorio, R.; Yamauti, M., Osorio, E., Ruiz-Requena, ME, Pashley, DH, Tay FR, Toledano, M.
The Role of Matrix metalloproteinases (MMPs) in Human Caries
C. Chaussain-Miller, F. Fioretti, M. Goldberg and S. Menashi J DENT RES 2006 85: 22