Restor Dent Endod.  2020 Aug;45(3):e31. 10.5395/rde.2020.45.e31.

Inhibition of matrix metalloproteinases: a troubleshooting for dentin adhesion

• Moraes IQSd
• Nascimento TGd
• Silva ATd
• Silva de Lira LMS
• Parolia A
• Moraes Porto ICCd

• KMID: 2512022
• DOI: http://doi.org/10.5395/rde.2020.45.e31

Abstract

Matrix metalloproteinases (MMPs) are enzymes that can degrade collagen in hybrid layer and reduce the longevity of adhesive restorations. As scientific understanding of the MMPs has advanced, useful strategies focusing on preventing these enzymes' actions by MMP inhibitors have quickly developed in many medical fields. However, in restorative dentistry, it is still not well established. This paper is an overview of the strategies to inhibit MMPs that can achieve a long-lasting material-tooth adhesion. Literature search was performed comprehensively using the electronic databases: PubMed, ScienceDirect and Scopus including articles from May 2007 to December 2019 and the main search terms were “matrix metalloproteinases”, “collagen”, and “dentin” and “hybrid layer”. MMPs typical structure consists of several distinct domains. MMP inhibitors can be divided into 2 main groups: synthetic (syntheticpeptides, non-peptide molecules and compounds, tetracyclines, metallic ions, and others) and natural bioactive inhibitors mainly flavonoids. Selective inhibitors of MMPs promise to be the future for specific targeting of preventing dentin proteolysis. The knowledge about MMPs functionality should be considered to synthesize drugs capable to efficiently and selectively block MMPs chemical routes targeting their inactivation in order to overcome the current limitations of the therapeutic use of MMPs inhibitors, i.e., easy clinical application and long-lasting effect.

Keyword

Matrix metalloproteinases; Collagen; Dentin; Hybrid layer

Figure

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  Figure 1 Structural organization of type I collagen fibril. (A) Two α1 and one α2 chains intertwine in a triple helix, giving rise to a collagen molecule. (B) Five adjacent helical molecules join together to form a microfibril. (C) Microfibrils meet in concentric bundles known as collagen fibrils. The crosslinking agents reinforce this bonding through the formation of crosslinks (represented in red and yellow) at the molecular and fibrillar levels, improving the mechanical properties of the demineralized collagen matrix.

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  Figure 2 Structure and activation of metalloproteinases. (A) Metalloproteinases are composed of an N-terminal propeptide, catalytic domain, hinge region and C-terminal hemopexin domain. Its activation occurs when cysteine-zinc coordination is lost as a consequence of the activation of the proteases that were in latent form (proenzymes) in the tissue. (B) After activation, collagenase cleaves the collagen molecules, causing them to lose the triple helical conformation, resulting in 1/4 and 3/4 length fragments that will be slowly hydrolysed by the gelatinases.

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