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Dentine Matrix Contains Sequestered Signalling Molecules

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While the major dentine inorganic component is hydroxyapatite, its organic matrix is mainly composed of collagen I and non-collagenous proteins such as dentine sialoprotein [18] and dentine matrix protein-1 [19]. These are involved in the initiation and the regulation of dentine mineralisation. In addition, different signalling molecules have been reported to be secreted by the odontoblasts and sequestered in the dentine matrix, mainly in an inactive form. Among others, these include transforming growth factor-β1 (TGF-β1), basic fibroblast growth factor (FGF-2), vascular endothelial growth factor (VEGF), and platelet derived growth factor (PDGF) [20, 21]. During the carious dissolution of the dentine matrix, these molecules can be released and reach the underlying odontoblasts leading to the upregulation of their synthetic activity.

In addition to the responsiveness to these growth factors, recent data demonstrated that odontoblasts act as sensor cells as they express transient potential channel receptors. These receptors allow the odontoblast to be responsive to the external stimulations, such as noxious heat, noxious cold, as well as chemical and mechanical stimulations [22]. Thus, upon stimulation, odontoblasts synthesise a new tertiary dentine at the pulp periphery facing the stimulation site. This focally secreted dentine can also be deposited within the dentine tubules to decrease their permeability to cariogenic bacteria and their toxins, leading to the protection of the underlying pulp.

Thus, odontoblasts represent the first defence mechanism in case of carious lesion development. Indeed, these cells also express receptors called Toll-like receptors (TLRs) 2 and 4 [23, 24], which recognise specific structures on Gram-positive and Gram-negative bacteria, respectively. These TLRs belong to a big family of pattern recognition receptors that are activated after contact with common molecules on the pathogen surface. In moderate carious injuries, TLRs 2 are highly expressed in the underlying odontoblasts [25]. Upon activation, these TLRs induce the secretion of antimicrobial molecules such as β-defensins and nitric oxide by the odontoblasts which have an antibacterial effect against S. mutans, thus limiting cariogenic bacteria progression towards the pulp [26]. Also, upon activation of their receptors, odontoblasts secrete proinflammatory chemokines which lead to dendritic cell recruitment in order to eliminate the pathogenic agents [27].

Overall, in the case of moderate dentine carious lesions, the odontoblasts act as a barrier exerting antimicrobial effects and initiating the secretion of a tertiary dentine to protect the underlying pulp (Fig. 3).

However, in the case of severe and rapidly progressive carious lesions, tertiary dentine focal synthesis may not be enough and bacteria may destroy the newly synthesised tertiary dentine, reach the underlying pulp, and induce an inflammatory reaction (Fig. 4).

Caries Excavation: Evolution of Treating Cavitated Carious Lesions

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