Abstract
Nerve growth factor (NGF) is a key regulator of the development and differentiation of neuronal and non-neuronal cells. In the present study we examined the distribution of NGF and its low and high-affinity receptors, p75NTR and TrkA respectively, in permanent human teeth under normal and pathological conditions. In intact functional teeth, NGF, p75NTR and TrkA are weakly expressed in dental pulp fibroblasts and odontoblasts that are responsible for dentine formation, while the NGF and p75NTR molecules are strongly expressed in nerve fibres innervating the dental pulp. In carious and injured teeth NGF and TrkA expression is upregulated in a selective manner in odontoblasts surrounding the injury sites, indicating a link between NGF signalling and dental tissue repair events. Accordingly, NGF and TrkA expression is strongly upregulated in cultured primary human dental mesenchymal cells during their differentiation into odontoblasts. Targeted release of NGF in cultured human tooth slices induced extensive axonal growth and migration of Schwann cells towards the NGF administration site. These results show that NGF signalling is strongly linked to pathological and regenerative processes in human teeth and suggest a potential role for this neurotrophic molecule in pulp regeneration.
Highlights
Nerve growth factor (NGF) is the first identified member of a family of neurotrophic molecules that comprises the brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), NT-4, and NT-6
The most intense NGF labelling was detected in the odontoblastic processes, while the staining was weaker in the odontoblastic bodies (Fig. 1D)
NGF staining was absent in dental pulp fibroblasts (Fig. 1D,G), NGF immunoreactivity was seen sporadicly in some of these cells (Fig. 1I)
Summary
Nerve growth factor (NGF) is the first identified member of a family of neurotrophic molecules that comprises the brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), NT-4, and NT-6. Dogs have shown that expression of NGF and p75NTR increased after dental injury, suggesting additional roles for NGF in regenerative processes[18, 19, 28, 29] All these findings illustrate the importance of NGF signalling in a variety of biological processes linked to tooth development, homeostasis and repair, only very few studies have been realized in human teeth to date. We examined the effects of NGF on neuronal sprouting in an in vitro dental slice culture model
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