Dentin Degradation: From Tissue Breakdown to Possibilities for Therapeutic Intervention

Abstract

Purpose of the review: Presently, dental materials science is driven by the search for new and improved materials that can trigger specific reactions from the affected tissue to stimulate repair or regeneration while interacting with the oral environment to promote or maintain oral health. In parallel, evidence from the past decades has challenged the exclusive role of bacteria in dentin tissue degradation in caries, questioning our understanding of caries etiopathogenesis. The goal of this review is to recapitulate the current evidence on the host and bacterial contributions to degradation, inflammation, and repair of the dentin-pulp complex in caries.

Recent findings: Contrasting findings attribute dentin breakdown to the activity of endogenous enzymes, such as matrix metalloproteinases (MMPs) and cathepsins, while the role of bacteria and their by-products in the destruction of dentin organic matrix and pulp inflammation has been for decades supported as an incontestable paradigm. Aiming to better understand the mechanisms involved in collagen degradation by host enzymes in caries, studies have showed that these proteinases are expressed in the mature dentin (i.e., after dentin formation) and become activated by the low pH in the acidic environment resulted by bacterial metabolism in caries. However, different host sources other than dentin-bound proteinases seem to also contribute to caries progression, such as saliva and pulp. Interestingly, studies evaluating pulp responses to bacteria invasion and inflammation in caries report higher levels of MMPs and cathepsins in inflamed tissue, but also showed MMP potential to resolve inflammation and stimulate wound healing. Notably, as reported for other tissues, MMPs exert dual roles in the dentin-pulp complex in caries, participating or regulating both degradative and reparative mechanisms.

Summary: The specific roles of host and bacteria and their by-products in caries progression have yet to be clarified. The complex interactions between inflammation and repair in caries pose challenges to a clear understanding of the dentin-pulp complex responses and changes to bacteria invasion. However, it opens new venues for the development of novel therapies and dental biomaterials based on the modulation of specific mechanisms to favor tissue repair and healing.

Keywords: Cathepsins; Dental caries; Dental pulp; Dentin; Extracellular matrix; Matrix metalloproteinases.

Fig. 1

Changes in the levels/activity of MMPs and cysteine cathepsins in dentin-pulp complex and the associated degradative (in red) and reparative (in blue) mechanisms. Caries progression into dentin exposes MMPs from the dentin matrix resulting in higher levels of these enzymes in carious tissue [–40, 83]. Following demineralization, bacterial acids can activate MMPs to start degradation of the dentin organic matrix [16]. The acidic environment can also activate cysteine cathepsins present in the dentin [18], which in turn have the potential to both degrade collagen as well as activate other dentinal MMPs. In addition, the acids from bacteria, by promoting dentin demineralization, release bioactive components from the matrix that can stimulate pulp response and repair [57]. Other bioactive molecules can also be released from the dentin matrix after its digestion by some MMPs [75••]. In pulp, as bacteria invasion progresses, by-products stimulate different cells in the pulp tissue to express higher levels of MMPs, which are involved in pulp extracellular matrix degradation and tissue inflammation [69, 70]