Adaptive Calcified Matrix Response of Dental Pulp to Bacterial Invasion Is Associated with Establishment of a Network of Glial Fibrillary Acidic Protein+/Glutamine Synthetase+ Cells

Abstract

We report evidence for anatomical and functional changes of dental pulp in response to bacterial invasion through dentin that parallel responses to noxious stimuli reported in neural crest-derived sensory tissues. Sections of resin-embedded carious adult molar teeth were prepared for immunohistochemistry, in situ hybridization , ultrastructural analysis , and microdissection to extract mRNA for quantitative analyses. In odontoblasts adjacent to the leading edge of bacterial invasion in carious teeth , expression levels of the gene encoding dentin sialo-protein were 16-fold greater than in odontoblasts of healthy teeth, reducing progressively with distance from this site of the carious lesion. In contrast , gene expression for dentin matrix protein-1 by odontoblasts was completely suppressed in carious teeth relative to healthy teeth. These changes in gene expression were related to a gradient of deposited reactionary dentin that displayed a highly modified structure. In carious teeth , interodontoblastic dentin sialo-protein ؊ cells expressing glutamine synthetase (GS) showed up-regulation of glial fibrillary acidic protein (GFAP

Glial Network Responses to Polymicrobial Invasion of Dentin

“…Considering both expression profile and anatomical proximity to odontoblasts, seracytes may play a role in modulating the reported plasticity of the odontoblastic layer [Hattyasy, 1961;Byers et al, 2003;Mitsiadis et al, 2011] possibly by neural differentiation [Anthony et al, 2004] that is compatible with the extensive networks formed in response to caries. Thus, while odontoblasts in mature teeth have been considered as terminally differentiated cells, they show remarkable adaptation to carious insult, particularly in the synthesis of reactionary dentin in a gradient of response extending from the zone of most extensive microbial penetration of dentin [Farahani et al, 2010;Charadram et al, 2012Charadram et al, , 2013. Evidence was obtained that GFAP + networks mediated this gradient response [Farahani et al, 2010].…”

“…Thus, while odontoblasts in mature teeth have been considered as terminally differentiated cells, they show remarkable adaptation to carious insult, particularly in the synthesis of reactionary dentin in a gradient of response extending from the zone of most extensive microbial penetration of dentin [Farahani et al, 2010;Charadram et al, 2012Charadram et al, , 2013. Evidence was obtained that GFAP + networks mediated this gradient response [Farahani et al, 2010].…”

“…An important aspect of the adaptive response of odontoblasts to carious insult is the synthesis of reactionary dentin [Smith et al, 1995[Smith et al, , 2001. The synthesis of reactionary dentin demands up-regulation of metabolic activity of odontoblasts [Lee et al, 2006;Farahani et al, 2010]. Carious insult results, initially, in up-regulation of the message for HIF-1α, interpreted as indicating hypoxic stress in responding odontoblasts.…”

“…Of note, reactionary dentin is deposited in a gradient decreasing in depth according to distance from the zone of microbial invasion. This response is mediated by odontoblasts that paradoxically down-regulate inter-odontoblastic junctions but that show extensive gap junction formation with adjacent glial cells [Farahani et al, 2010]. Accordingly, it is proposed that glial networks control the gradient response of reactionary dentin formation.…”

Ex vivo detection and characterization of remineralized carious dentin, by nanoindentation and single point Raman spectroscopy, after amalgam restoration

“…Proteoglycans and glycosaminoglycans (or shape modulus complexes-lipids and proteolipids) participate in biomineralization via the action of the highly negatively charged glycosaminoglycan side chains in recruiting and stabilizing positively charged calcium ions, conducting a biological signaling role [2] . This function would be involved in the signaling mechanisms that activate the odontoblast response during dentin remineralization, in disease [2,41,55] . Dentin remineralization has been achieved after submitting the caries affected dentin substrata to Zn-containing amalgam restorations and thermocycling, as stated above.…”