Disclosing the physiology of pulp tissue for vital pulp therapy

Abstract

The discovery that dentine is a reservoir of bioactive molecules that can be recruited on demand has attracted efforts to develop new protocols and materials for vital pulp therapy (VPT). The noncollagenous proteins (NCPs) present in the dentine extracellular matrix (ECM) include growth factors (TGF-β1, BMP-7, FGF-2, IGF-1 and IGF-2, NGF and GDNF), extracellular matrix molecules (DSP, DPP, BSP, DMP-1 and DSPP) and both anti-inflammatory and pro-inflammatory chemokines and cytokines (TNF-α, IL-1, IL-6 and IL-10). Molecules such as DSP and DPP are mainly expressed by odontoblasts, and they are cleaved products from dentine sialophosphoprotein (DSPP). Some molecules, such as TGF-β1, specifically interact with decorin/biglycan in dentine. Although TGF-β1 increases the expression and secretion of NGF in human pulp cells, NGF induces mineralization and increases the expression of DSPP and DMP-1. Furthermore, GDNF may act as a cell survival factor and mitogen during tooth injury and repair. Pulp capping materials, such as MTA and calcium hydroxide, can solubilize bioactive dentine molecules (TGF-β1, NGF and GDNF) that stimulate tertiary dentinogenesis. The binding of these signalling molecules leads to activation of several signalling transduction pathways involved in dentinogenesis, odontoblast differentiation and inflammatory responses, such as the p38 MAPK, NF-kβ and Wnt/β-catenin signalling pathways. Understanding the cascade of cellular and molecular events underlying the repair and regeneration processes provides a reasonable new approach to VPT through a targeted interaction between tooth tissue and bioactive molecules.

Calcific metamorphosis of pulp after extrusive luxation

“…This dentin was produced both by odontoblasts from the pre‐existing odontoblast layer, and from those cells that had differentiated from the mesenchymal cells present in the pulp . Stress of pulp cells caused by hypoxia triggers the production and release of growth factors that stimulate different types of cells . Consequently, pulp cells undergo metaplasia and the production of dentin in a disordered and random manner, far from the pulp walls.…”

“…[9][10][11][12] Stress of pulp cells caused by hypoxia triggers the production and release of growth factors that stimulate different types of cells. [19][20][21][22] Consequently, pulp cells undergo metaplasia and the production of dentin in a disordered and random manner, far from the pulp walls.…”

Molecular Mechanisms of Dentine-Pulp Complex Response Induced by Microbiome of Deep Caries

“…This complex cocktail of bioactive molecules, commonly based on noncollagenous proteins is characterized by components such as growth factors (Figure 2), neurotrophic factors (Figure 3), extracellular matrix molecules ( Figure 4), cytokines, neuropeptides, and others (6).…”

“…The best investigated growth factors aiming to induce this process are transforming growth factor β-1 (TGF-β1), bone morphogenetic protein-2 (BMP-2), bone morphogenetic protein-4 (BMP-4), bone morphogenetic protein-7 (BMP-7), fibroblast growth factor-2 (FGF-2), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-2 (IGF-2). However, it seems that even the activity of main growth factors as TGF-β1, BMP-2 and FGF-2 at their turn is regulated directly or indirectly by extracellular matrix protein PLAP-1 that is released in periodontal ligament ( Figure 2) (6,20).…”

“…As known all pulp injuries occurred during caries activity and its subsequent conservative treatment aiming to preserve the vitality are producing local histological modifications in dentin-pulp complex including the tertiary dentin development. In recent years the advances in biomarkers and stem cells field opened a new window to understanding the molecular mechanisms that regulate the tertiary dentin secretion and mineralization (6).…”