Developmental growth and degeneration of pulpal axons in feline primary incisors

Fried, Kaj; Hildebrand, Claes

doi:10.1002/cne.902030105

Cited by 50 publications

(8 citation statements)

References 37 publications

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“…Thus, there is a very dynamic pattern of axonal targeting through the shift from primary (deciduous) to permanent dentition, and during the maturation of each of these sets of teeth. 62 The process of dental innervation during developmental maturation of teeth has been shown to be elegantly modulated by a cascade of molecular signals. 18 Primary afferent branches accumulate around the apical papilla, but do not enter the dental pulp proper until late in the cap stage of tooth development to finalize the branching of the primary afferents on the periphery of the pulp-dentin complex.…”

Section: Discussionmentioning

confidence: 99%

Stem Cells of the Apical Papilla Regulate Trigeminal Neurite Outgrowth and Targeting through a BDNF-Dependent Mechanism

Almeida

Chen

Henry

et al. 2014

Tissue Engineering Part A

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Regenerative endodontic procedures have become a valuable alternative for the treatment of immature teeth with pulp necrosis. In addition to resolution of periradicular pathosis and promotion of continued root development, positive vitality testing has been observed in some regenerative clinical cases. Importantly, the positive response to electric stimulation of the regenerated tissue requires targeting of periradicular axons into the previously empty root canal space. However, the mechanism by which this process occurs is largely unknown. Since stem cells of the apical papilla (SCAP) have been proposed to populate the root canal following regenerative endodontic procedures, we hypothesized that SCAP regulate neurite outgrowth and axonal targeting. To test this hypothesis, we established primary co-cultures of human SCAP and rat trigeminal neurons, and performed neurite outgrowth assays using ELISA and confocal microscopy to determine the effect of increasing concentration of SCAP on the total neurite outgrowth and axonal targeting. In addition, we evaluated whether SCAP evoked axonal targeting in vivo using a matrigel subcutaneous implant assay. Data were analyzed by ANOVA with Bonferroni's post hoc test, and significance was set at p < 0.05. The results demonstrated that SCAP release a soluble factor that regulates neurite outgrowth from cultured trigeminal neurons. Next, we demonstrated that this effect is completely abolished by pretreatment with a neutralizing antibody to brain-derived neurotrophic factor (BDNF), but not by antibodies to other neurotrophins. Further, SCAP release BDNF in a concentration-dependent manner as detected by ELISA, and trigger directed axonal targeting both in vitro and in vivo as demonstrated by microfluidic and matrigel implant experiments, respectively. Collectively, these results suggest that SCAP may be responsible for the chemical signal driving axons to target regenerated tissue via a BDNF-dependent mechanism.

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Section: Discussionmentioning

confidence: 99%

Stem Cells of the Apical Papilla Regulate Trigeminal Neurite Outgrowth and Targeting through a BDNF-Dependent Mechanism

Almeida

Chen

Henry

et al. 2014

Tissue Engineering Part A

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“…Little is known about the history of prospective pulpal afferents during the interval between the establishment prenatally of permanent trigeminal ganglion cell numbers (Davies and Lumsden, 1984; Ashwell and Waite, 1991; White et al, 1995) and the onset of pulpal innervation, an event that begins postnatally concurrent with the apposition of dentin and enamel of the tooth crown (Corpron and Avery, 1973; Johnsen and Karlsson, 1977; Fried and Hildebrand, 1981a,1981b; Mohamed and Atkinson, 1983; Tsuzuki and Kitamura, 1991; Christensen et al, 1993). The ingrowth of nerve fibers into the pulp is a protracted process that, in the rat, begins several days after birth for the incisor and 1st and 2nd molars (Tsuzuki and Kitamura, 1991; Fristad et al, 1994; present study) and at about 3 weeks after birth for the late developing 3rd molar (Byers, 1980).…”

Section: Discussionmentioning

confidence: 99%

Course and composition of the nerves that supply the mandibular teeth of the rat

et al. 1999

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The rodent dentition has become an important model for investigations of interactions between dental tissues and peripheral neurons. Although experimental nerve injury has been widely used for such studies, there is uncertainty about the courses of nerve fibers supplying the mandibular teeth. In order to clarify this, we used a mixture of monoclonal antibodies against neurofilament proteins to enhance demonstration of nerve fibers so that small nerves could be readily traced in serial frozen sections of mandibles of Sprague Dawley rats ranging in age from embryonic day (E) 18 to postnatal day (P) 90. The 1st molar and anterior portion of the 2nd molar were innervated by small nerves that emerged as distinct branches of the IAN trunk at or near the mandibular foramen. In contrast, the nerve supply to the 3rd molar and posterior part of the 2nd molar was a branch of the lingual nerve that bypassed the mandibular canal altogether. The IAN trunk split into the mental nerve and a large branch to the incisor about 2 mm anterior to the mandibular foramen. Thick branches of the incisor nerve descended into the incisor socket to form a dense plexus of nerve fiber bundles extending along the length of the incisor periodontium. The sparse pulpal innervation of the incisor was provided by a few thin fascicles that emerged from the caudal portion of the periodontal plexus to enter the incisor apex. The dental branches of the IAN and lingual nerve seen in the adult were well established and readily identifiable at age E18 even though their targets were limited to the follicles of the developing teeth. These studies show that the trigeminal branches that supply the mandibular teeth can be identified at a wide range of ages as distinct nerves at a considerable distance proximal to their targets. This detailed information on the courses taken by the dental nerves can provide an anatomical basis for increased precision in characterization and perturbation of neural pathways from the molars and incisor.

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“…Fried & Hildebrand [10] used electron microscopy to describe and count the pulpal nerve supply of fully formed and resorbing feline incisors. They showed that the nerve supply varies with the age of the tooth.…”

Section: Discussionmentioning

confidence: 99%

On the pulpal nerve supply in primary human teeth: evidence for the innervation of primary dentine*

Egan

Hector

Bishop

1999

Int J Paed Dentistry

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The presence of nerves in human tooth pulp has been recognized for over a hundred years, and the innervation of dentine for about 40 years. These observations have been made in permanent teeth. Very few studies have reported on the innervation of the primary pulp and dentine. The purpose of this study was to describe the innervation of the primary tooth pulp-dentine complex. Ten mature primary teeth (one incisor, six canines and three molars) were used. Immediately following extraction they were divided into three sections using a diamond disc and saline coolant. They were then immersion fixed in a solution of formaldehyde and picric acid dissolved in a phosphate buffer pH 7.4). The teeth were then demineralized for 1-3 weeks in formic acid. Following complete demineralization, 30 microns sections were cut on a freezing microtome. Neural tissue was stained using a specific antibody to calcitonin gene related peptide (CGRP). Sections were mounted on glass slides and examined using light microscopy. No individual nerve fibres were seen in the control sections, suggesting that the method used was specific for CGRP-containing nerve fibres. The primary teeth appeared to be well innervated. Myelinated and unmyelinated nerves were seen. There was a dense but variable subodontoblastic plexus of nerves (plexus of Raschkow) and nerve fibres were seen to leave this to travel towards the odontoblast layer. Most terminated here, but a few penetrated the odontoblast layer to enter predentine and the dentine tubules. The maximum penetration was 125 microns but most terminated within 30 microns of the dentinopulpal junction. The coronal region was more densely innervated than the root. Within the crown the cervical third was the most densely innervated region, followed by the pulp horn and the middle third. In conclusion, this study has demonstrated that mature primary tooth contains a pulp which is well innervated and has many nerve endings terminating in or near the odontoblast layer, with a small number penetrating into dentine.

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Developmental growth and degeneration of pulpal axons in feline primary incisors

Cited by 50 publications

References 37 publications

Stem Cells of the Apical Papilla Regulate Trigeminal Neurite Outgrowth and Targeting through a BDNF-Dependent Mechanism

Stem Cells of the Apical Papilla Regulate Trigeminal Neurite Outgrowth and Targeting through a BDNF-Dependent Mechanism

Course and composition of the nerves that supply the mandibular teeth of the rat

On the pulpal nerve supply in primary human teeth: evidence for the innervation of primary dentine*

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