IGF-1 Mediates EphrinBl Activation in Regulating Tertiary Dentin Formation

S. Matsumura, A. Quispe-Salcedo, C. M. Schiller, J. S. Shin, B. M. Locke, Shoshana Yakar, E. Shimizu

Research output: Contribution to journalArticle

Abstract

Eph receptors belong to a subfamily of receptor tyrosine kinases that are activated by membrane-spanning ligands called ephrins. Previously, we demonstrated that the ephrinB1-EphB2 interaction regulates odontogenic/osteogenic differentiation from dental pulp cells (DPCs) in vitro. The goal of this study was to identify the molecular mechanisms regulated by the EphB2/ephrinB1 system that govern tertiary dentin formation in vitro and in vivo. During tooth development, ephrinB1, and EphB2 were expressed in preodontoblast and odontoblasts at postnatal day 4. EphrinB1 was continuously expressed in odontoblasts and odontoblastic processes until the completion of tooth eruption. In addition, ephrinB1 was expressed in odontoblastic processes 2 wk following tooth injury without pulp exposure, whereas EphB2 was expressed in the center of pulp niches but not odontoblasts. In a model of tooth injury with pulp exposure, ephrinB1 was strongly expressed in odontoblasts 4 wk postinjury. In vitro studies with human and mouse DPCs treated with calcium hydroxide (CH) or mineral trioxide aggregate (MTA) showed an increased expression of insulin-like growth factor 1 (IGF-1). Experiments using several inhibitors of IGF-1 receptor signaling revealed that inhibiting the Ras/Raf-1/MAPK pathway inhibited EphB2 expression, and inhibiting the PI3K/Akt/mTOR pathway specifically inhibited ephrinB1 gene expression. Tooth injury in mice with odontoblast-specific IGF-1 receptor ablation exhibited a reduced tertiary dentin volume, mineral density, and ephrinB1 expression 4 wk following injury. We conclude that the IGF-1/ephrinB1 axis plays significant roles in the early stages of tooth injury. Further research is needed to fully understand the potential of targeting ephrinB1 as a regenerative pulp therapy.

Original languageEnglish (US)
Pages (from-to)1153-1161
Number of pages9
JournalJournal of Dental Research
Volume96
Issue number10
DOIs
StatePublished - Sep 1 2017

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Odontoblasts
Tooth Injuries
Somatomedins
Dentin
Somatomedin Receptors
Dental Pulp
Eph Family Receptors
Ephrins
Tooth Eruption
Calcium Hydroxide
Receptor Protein-Tyrosine Kinases
Phosphatidylinositol 3-Kinases
Minerals
Tooth
Ligands
Gene Expression
Membranes
Wounds and Injuries
Research
In Vitro Techniques

Keywords

  • cell signaling
  • dentinogenesis
  • histochemistry
  • odontogenesis
  • pulp biology
  • stem cell(s)

ASJC Scopus subject areas

  • Dentistry(all)

Cite this

Matsumura, S., Quispe-Salcedo, A., Schiller, C. M., Shin, J. S., Locke, B. M., Yakar, S., & Shimizu, E. (2017). IGF-1 Mediates EphrinBl Activation in Regulating Tertiary Dentin Formation. Journal of Dental Research, 96(10), 1153-1161. https://doi.org/10.1177/0022034517708572

IGF-1 Mediates EphrinBl Activation in Regulating Tertiary Dentin Formation. / Matsumura, S.; Quispe-Salcedo, A.; Schiller, C. M.; Shin, J. S.; Locke, B. M.; Yakar, Shoshana; Shimizu, E.

In: Journal of Dental Research, Vol. 96, No. 10, 01.09.2017, p. 1153-1161.

Research output: Contribution to journalArticle

Matsumura, S, Quispe-Salcedo, A, Schiller, CM, Shin, JS, Locke, BM, Yakar, S & Shimizu, E 2017, 'IGF-1 Mediates EphrinBl Activation in Regulating Tertiary Dentin Formation', Journal of Dental Research, vol. 96, no. 10, pp. 1153-1161. https://doi.org/10.1177/0022034517708572
Matsumura S, Quispe-Salcedo A, Schiller CM, Shin JS, Locke BM, Yakar S et al. IGF-1 Mediates EphrinBl Activation in Regulating Tertiary Dentin Formation. Journal of Dental Research. 2017 Sep 1;96(10):1153-1161. https://doi.org/10.1177/0022034517708572
Matsumura, S. ; Quispe-Salcedo, A. ; Schiller, C. M. ; Shin, J. S. ; Locke, B. M. ; Yakar, Shoshana ; Shimizu, E. / IGF-1 Mediates EphrinBl Activation in Regulating Tertiary Dentin Formation. In: Journal of Dental Research. 2017 ; Vol. 96, No. 10. pp. 1153-1161.
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