TY - JOUR
T1 - Expression of Neurotrophic Factors in Human Dentin and Their Regulation of Trigeminal Neurite Outgrowth
AU - Austah, Obadah
AU - Widbiller, Matthias
AU - Tomson, Phillip L.
AU - Diogenes, Anibal
N1 - Funding Information:
This research was supported in part by a research grant from the Foundation for Endodontics.
Publisher Copyright:
© 2018 American Association of Endodontists
PY - 2019/4
Y1 - 2019/4
N2 - Introduction: Neurotrophic factors play a significant role in the innervation of the pulp-dentin complex during and after organogenesis. There have been numerous bioactive molecules identified in the dentin extracellular matrix; however, the expression of neurotrophic factors in the dentin matrix and their biological activity are largely unknown. The purpose of this study was to characterize the relative expression of neurotrophic factors in human dentin matrix proteins (DMPs) and their effect on neurite outgrowth of trigeminal (TG) neurons. Methods: Dentin was powdered in liquid nitrogen from noncarious human third molar teeth. DMPs were solubilized through an EDTA extraction method, dialyzed, and lyophilized until use. The relative expression of nerve growth factor, brain-derived neurotrophic factor, glial cell−line derived neurotrophic factor, neurotrophin 3, and neurotrophin 4/5 was determined by the enzyme-linked immunosorbent assay. Rat TG neurons were cultured and exposed to different concentrations of DMPs (1–10 5 ng/mL) or vehicle, and a quantitative neurite outgrowth assay was performed. Results: Human DMPs contained all of the tested neurotrophic factors, with glial cell−line derived neurotrophic factor and neurotrophin 4/5 found at the highest levels. DMPs were able to promote the neurite outgrowth of rat TG neurons at an optimum concentration of 10–10 2 ng/mL, whereas the effect was partially inhibited at higher concentrations (>10 3 ng/mL). Conclusions: The human dentin extracellular matrix is a rich reservoir for neurotrophic factors that are key components for neuronal homeostasis, differentiation, and regeneration. These data suggest that neurotrophins in DMPs could play an important role as signaling molecules for the innervation of the pulp-dentin complex during the processes of tooth formation, repair, and regeneration.
AB - Introduction: Neurotrophic factors play a significant role in the innervation of the pulp-dentin complex during and after organogenesis. There have been numerous bioactive molecules identified in the dentin extracellular matrix; however, the expression of neurotrophic factors in the dentin matrix and their biological activity are largely unknown. The purpose of this study was to characterize the relative expression of neurotrophic factors in human dentin matrix proteins (DMPs) and their effect on neurite outgrowth of trigeminal (TG) neurons. Methods: Dentin was powdered in liquid nitrogen from noncarious human third molar teeth. DMPs were solubilized through an EDTA extraction method, dialyzed, and lyophilized until use. The relative expression of nerve growth factor, brain-derived neurotrophic factor, glial cell−line derived neurotrophic factor, neurotrophin 3, and neurotrophin 4/5 was determined by the enzyme-linked immunosorbent assay. Rat TG neurons were cultured and exposed to different concentrations of DMPs (1–10 5 ng/mL) or vehicle, and a quantitative neurite outgrowth assay was performed. Results: Human DMPs contained all of the tested neurotrophic factors, with glial cell−line derived neurotrophic factor and neurotrophin 4/5 found at the highest levels. DMPs were able to promote the neurite outgrowth of rat TG neurons at an optimum concentration of 10–10 2 ng/mL, whereas the effect was partially inhibited at higher concentrations (>10 3 ng/mL). Conclusions: The human dentin extracellular matrix is a rich reservoir for neurotrophic factors that are key components for neuronal homeostasis, differentiation, and regeneration. These data suggest that neurotrophins in DMPs could play an important role as signaling molecules for the innervation of the pulp-dentin complex during the processes of tooth formation, repair, and regeneration.
KW - Dentin matrix protein
KW - dentinogenesis
KW - neurite outgrowth
KW - neurotrophic factors
KW - neurotrophins
KW - regeneration
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U2 - 10.1016/j.joen.2018.12.011
DO - 10.1016/j.joen.2018.12.011
M3 - Article
C2 - 30771898
AN - SCOPUS:85061447894
SN - 0099-2399
VL - 45
SP - 414
EP - 419
JO - Journal of Endodontics
JF - Journal of Endodontics
IS - 4
ER -