Dental Pulp Defence and Repair Mechanisms in Dental Caries - PubMed (original) (raw)

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Dental Pulp Defence and Repair Mechanisms in Dental Caries

Jean-Christophe Farges et al. Mediators Inflamm. 2015.

Abstract

Dental caries is a chronic infectious disease resulting from the penetration of oral bacteria into the enamel and dentin. Microorganisms subsequently trigger inflammatory responses in the dental pulp. These events can lead to pulp healing if the infection is not too severe following the removal of diseased enamel and dentin tissues and clinical restoration of the tooth. However, chronic inflammation often persists in the pulp despite treatment, inducing permanent loss of normal tissue and reducing innate repair capacities. For complete tooth healing the formation of a reactionary/reparative dentin barrier to distance and protect the pulp from infectious agents and restorative materials is required. Clinical and in vitro experimental data clearly indicate that dentin barrier formation only occurs when pulp inflammation and infection are minimised, thus enabling reestablishment of tissue homeostasis and health. Therefore, promoting the resolution of pulp inflammation may provide a valuable therapeutic opportunity to ensure the sustainability of dental treatments. This paper focusses on key cellular and molecular mechanisms involved in pulp responses to bacteria and in the pulpal transition between caries-induced inflammation and dentinogenic-based repair. We report, using selected examples, different strategies potentially used by odontoblasts and specialized immune cells to combat dentin-invading bacteria in vivo.

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Figures

Figure 1

Figure 1

Two key aspects of the odontoblast defence against dentin-invading bacteria. Bacteria (B) present in the carious dentinal lesion release pathogenic components that activate (blue arrow) odontoblasts (dark blue) adjacent to the lesion, triggering the production of antibacterial molecules (blue dots). These molecules diffuse through dentin tubules in an attempt to destroy the invading microorganisms (NO, BDs) or considerably decrease their pathogenicity (LBP). In parallel, proinflammatory and immunomodulatory mediators (green dots), including IL-6, IL-10, CXCL1, CXCL2, CXCL8 (IL-8), CXCL10, and CCL2, are secreted by odontoblasts at the opposite cell pole and diffuse into the subodontoblast pulp area (green arrow) where they activate and mobilize various populations of immune cells (as described in the main text body) enabling the immunosurveillance of the tissue. Immune cells then migrate (dotted grey arrow) towards the pulp-dentin interface beneath the lesion to combat the bacteria and coordinate the immune defense response.

Figure 2

Figure 2

The putative role of dendritic cells (DCs) in the regulation of T helper (Th) and induced regulatory T (iTreg) cell differentiation. Upon encountering antigens (Ag), immature DCs usually become mature DCs which present antigens to naive CD4+ (Th0) cells. Upon antigen recognition, Th0 cells clonally expand and can differentiate into various subsets of effector cells (Th1, Th2, or Th17) or into iTreg cells depending on the cytokines present in their environment. Alternatively, immature DCs can mature only partially to become Tolerogenic-DCs (Tol-DCs) which can directly induce iTreg cell differentiation through TGF-β and IL-10 secretion. IL, interleukin; IFN, interferon; TGF, transforming growth factor; Ig, immunoglobulin.

Figure 3

Figure 3

Tables ((a) and (b)) showing the key functions associated with the 16 and 3 molecular networks identified as being significantly activated (≥ 6 focus genes) in carious and healthy pulpal tissue, respectively. Shading of boxes indicates the networks which associated with the function and hence supported its inclusion as being active. Analysis was performed using the Ingenuity Pathways Analysis (IPA) software (

http://www.ingenuity.com/products/ipa

) on the high-throughput datasets reported in McLachlan et al. [11]. Sixteen and three functional categories were identified as being activated in carious diseased and healthy pulpal tissues, respectively. Carious diseased pulp tissue clearly demonstrated increased molecular network and functional activity compared with healthy pulpal tissue. Asterisks (∗) in (a) indicate functions which are associated with immune system cells (as identified by IPA); notably some evidence of hard tissue repair function was also evident (#). Ontological functions identified in (b) likely associate with pulp tissue homeostatic processes. Image (c) shows an example network (network 1 from the carious pulp tissue dataset) which also shows the subcellular localisation of the molecules that were identified as differentially expressed. The activation of this network via intracellular signalling cascades results in the elaboration of key inflammatory-associated chemokines, such as CXCL8 (IL-8) and CCL2, and the matrix metalloproteinases (MMPs) 1 and 9.

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References

    1. Hamilton I. R. Ecological basis for dental caries. In: Kuramitsu H. K., Ellen R. P., editors. Oral Bacterial Ecology: The Molecular Basis. Wymondham, UK: Horizon Scientific Press; 2000. pp. 219–274.
    1. Farges J.-C., Keller J.-F., Carrouel F., et al. Odontoblasts in the dental pulp immune response. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution. 2009;312(5):425–436. doi: 10.1002/jez.b.21259. - DOI - PubMed
    1. Love R. M., Jenkinson H. F. Invasion of dentinal tubules by oral bacteria. Critical Reviews in Oral Biology and Medicine. 2002;13(2):171–183. doi: 10.1177/154411130201300207. - DOI - PubMed
    1. Cooper P. R., McLachlan J. L., Simon S., Graham L. W., Smith A. J. Mediators of inflammation and regeneration. Advances in dental research. 2011;23(3):290–295. doi: 10.1177/0022034511405389. - DOI - PubMed
    1. Heyeraas K. J., Berggreen E. Interstitial fluid pressure in normal and inflamed pulp. Critical Reviews in Oral Biology and Medicine. 1999;10(3):328–336. doi: 10.1177/10454411990100030501. - DOI - PubMed

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