Role of Host-Derived Proteinases in Dentine Caries and Erosion

Abstract

Demineralization in dentinal caries and erosion exposes dentine organic matrix. This exposed matrix, containing type I collagen and non-collagenous proteins, is then degraded by host collagenolytic enzymes, matrix metalloproteinases (MMPs) and cysteine cathepsins. The knowledge of the identities and function of these enzymes in dentine has accumulated only within the last 15 years, but has already formed a field of research called ‘dentine degradomics'. This research has demonstrated the role of endogenous collagenolytic enzymes in caries and erosion development. In demineralized dentine, the enzymes degrade triple-helical collagen molecules, leading to the gradual loss of collagen matrix. Even before that, they can cleave off the terminal non-helical ends of collagen molecules called telopeptides, leading to the structural changes at the intramolecular gap areas, which may affect or even prevent intrafibrillar remineralization, which is considered essential in restoring the dentine's mechanical properties. They may also cause the loss of non-collagenous proteins that could serve as nucleation sites for remineralization. Here we review the findings demonstrating that inhibition of salivary or dentine endogenous MMPs and cysteine cathepsins may provide preventive means against the progression of caries or erosion. Furthermore, we also suggest the future directions for the new experimental preventive research to gain more knowledge of the enzymes and their function during and after dentine demineralization, and the pathways to find the clinically acceptable means to prevent the functional activity of these enzymes.

Postradiation Matrix Metalloproteinase-20 Expression and Its Impact on Dental Micromorphology and Radiation-Related Caries

“…Recent studies have demonstrated that endogenous dentinal and salivary MMP can play a major role in dentinal caries and erosion pathology [Tjä-derhane et al, 1998;van Strijp et al, 2003;Buzalaf et al, 2015;Tjäderhane et al, 2015]. At least MMP-2, MMP-3, MMP-8, MMP-9, and MMP-20 have been indicated to participate in the process of dentin caries [Tjäderhane et al, 1998;Sulkala et al, 2002;Vidal et al, 2014].…”

Using Biomimetic Polymers in Place of Noncollagenous Proteins to Achieve Functional Remineralization of Dentin Tissues

“…The supersaturation is defined as σ = ln ((αCa 2+ ) 5 (αPO 4 3− ) 3 (αOH − )/ Ksp ), where α denotes the species activity, and Ksp denotes the equilibrium solubility constant at 25°C. This supersaturated (σ = 3.34) calcium phosphate solution was made by mixing 13.5 mM of CaCl 2 ·H 2 O with 6.3 mM of K 2 HPO 4 in equal volumes to achieve [Ca 2+ ]=6.75 mM and [HPO 4 2− ]=3.15 mM.…”

“…As caries penetrate the outer enamel, which contains little or no organic matrix, it begins to demineralize the underlying dentin, which consists of hydroxyapatite (HAP) nanocrystals located within collagen fibrils (intrafibrillar) and between collagen fibrils (extrafibrillar) 2 . The bacterial attack is also accompanied by the release of bacterial and endogenous proteases in dentin, which leads to hydrolysis of the collagen scaffold as well as the NCPs 3 . When remineralization is attempted, the absence of NCPs inhibits the development of intrafibrillar HAP.…”

Ecological Hypothesis of Dentin and Root Caries

“…Dentin itself is also known to contain proteases, such as MMP-2, 3, 8, 9, and 20, and cysteine cathepsins B and K [Sulkala et al, 2002;Mazzoni et al, 2009;Shimada et al, 2009;Toledano et al, 2010;Boushell et al, 2011;Buzalaf et al, 2015;Tjäderhane et al, 2015]. These proteases are produced during dentin formation and then become embedded in the dentin matrix (in their inactive forms) together with protease inhibitors, such as tissue inhibitor of metalloproteinases (TIMP)-1 and -2 [Ishiguro et al, 1994;Niu et al, 2011].…”