# Growth factors-induced dentinogenesis

> **NIH NIH R01** · RBHS-SCHOOL OF DENTAL MEDICINE · 2021 · $65,885

## Abstract

Project summary:
There is an increasing need to develop strategies for pulp regeneration therapy to overcome
tooth injury due to caries, restorative procedures, or trauma. Currently, there is a significant
gap in our understanding of the molecular and cellular mechanisms regulating reparative
dentinogenesis. Our long-term goal is to gain fundamental knowledge on the human dental pulp
cellular niche and to apply that knowledge to lessen the burdens of tooth injury due to caries,
restorative procedures, or trauma. The objective for this application is to elucidate how the
interactions between ephrinB1 and IGF-1 in the dental pulp niche induce dentinogenesis in vivo.
The overarching hypothesis is that IGF-1 regulates cells of the tooth pulp niche, and induces
dentinogenesis via ephrinB1. Guided by strong preliminary data, this hypothesis will be tested
by pursuing the following two specific aims: Aim 1: Determine the mechanism by which
ephrinB1 controls the number of odontoblast progenitors, their proliferation, and differentiation in
the tooth pulp. And Aim 2: Determine the cellular and molecular mechanisms by which IGF-1
regulates ephrinB1 expression in vivo using mouse models and ex vivo using human DPSCs
and human oral mucosa stem cells. An already-generated odontoblast-specific ephrinB1
knockout mouse lines (using cre driven by the DMP1 or osteocalcin promoters), and mouse
lines of IGF-1 receptor (DMP1-IGF-1RKO) and the hepatic IGF-1 transgenic (HIT) line will be
used to achieve the two aims. Importantly, initial characterization of our models indicates that
both IGF-1 and ephrinB1 involved in dentinogenesis in vivo. The proposed research is
conceptually innovative because we show, for the first time, the interactions between ephrinB1
and IGF-1 during dentinogenesis in vivo. Further, we offer a direct approach to determine these
interactions using unique mouse models, as well as primary human dental pulp cell cultures.
The proposed research is significant because it is expected to advance the field of regenerative
endodontic procedures and will impact the overall effort to retain the natural tertiary dentin
formation process following injury.

## Key facts

- **NIH application ID:** 10250621
- **Project number:** 3R01DE025885-06S1
- **Recipient organization:** RBHS-SCHOOL OF DENTAL MEDICINE
- **Principal Investigator:** Emi Shimizu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $65,885
- **Award type:** 3
- **Project period:** 2020-11-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10250621

## Citation

> US National Institutes of Health, RePORTER application 10250621, Growth factors-induced dentinogenesis (3R01DE025885-06S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10250621. Licensed CC0.

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