Abstract
The macroscopic and microscopic anatomy of the oral cavity is complex and unique in the human body. Soft-tissue structures are in close interaction with mineralized bone, but also dentine, cementum and enamel of our teeth. These are exposed to intense mechanical and chemical stress as well as to dense microbiologic colonization. Teeth are susceptible to damage, most commonly to caries, where microorganisms from the oral cavity degrade the mineralized tissues of enamel and dentine and invade the soft connective tissue at the core, the dental pulp. However, the pulp is well-equipped to sense and fend off bacteria and their products and mounts various and intricate defense mechanisms. The front rank is formed by a layer of odontoblasts, which line the pulp chamber towards the dentine. These highly specialized cells not only form mineralized tissue but exert important functions as barrier cells. They recognize pathogens early in the process, secrete antibacterial compounds and neutralize bacterial toxins, initiate the immune response and alert other key players of the host defense. As bacteria get closer to the pulp, additional cell types of the pulp, including fibroblasts, stem and immune cells, but also vascular and neuronal networks, contribute with a variety of distinct defense mechanisms, and inflammatory response mechanisms are critical for tissue homeostasis. Still, without therapeutic intervention, a deep carious lesion may lead to tissue necrosis, which allows bacteria to populate the root canal system and invade the periradicular bone via the apical foramen at the root tip. The periodontal tissues and alveolar bone react to the insult with an inflammatory response, most commonly by the formation of an apical granuloma. Healing can occur after pathogen removal, which is achieved by disinfection and obturation of the pulp space by root canal treatment. This review highlights the various mechanisms of pathogen recognition and defense of dental pulp cells and periradicular tissues, explains the different cell types involved in the immune response and discusses the mechanisms of healing and repair, pointing out the close links between inflammation and regeneration as well as between inflammation and potential malignant transformation.
Highlights
Introduction distributed under the terms and small, teeth are complex structures composed of several components with unique architectural characteristics and functions (Figure 1)
Odontoblasts, pulp fibroblasts, leukocytes and pulpal stem cells express pattern-recognition receptors (PRRs) [19,20,21,22], in particular Toll-like (TLR) and NOD-like receptors (NLR) [23], which indicates that the dental pulp is equipped to sense a wide variety of pathogens that could invade the pulp chamber
Antigen binding to TLR2 and the cytosolic NOD2 leads to the activation of nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (MPK) signaling, resulting in the production of proinflammatory cytokines and chemokines, which can recruit dendritic cells [5,19,25] and other immune cells towards the dentine-pulp interface beneath the carious lesion to neutralize bacterial toxins [26,27], and leading to an inhibition of dentinogenesis if the insult is severe [21,28]
Summary
These cells develop in the dorsal region of the neural tube and migrate into the. The presence of functional a collagenous matrix, which later mineralizes to form dentine This formative tissue is prerequisite for the completion of root formation. Each cell leaves a process behind, secrete a collagenous matrix, which later mineralizes to form dentine. This formative pro- which becomes embeddedand in the mineralized not tissue, giving dentine tubular structure. There is no physiological remodeling replacement of dentine Due to dentine, they are the first line of cells to get in contact with toxins and compounds of oral bacteria once the mineralized matrices have started to break down, with caries being the origin from neural crest-derived ectomesenchyme and their unique localization, odonto ofby blasts feature many more characteristics than just those of mineralizing cells. Dentine-pulp complex (own collection). (B) Odontoblast layer depicted by scanning electron microscopy (modified from [12])
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