# Growth factors-induced dentinogenesis

> **NIH NIH R01** · RBHS-SCHOOL OF DENTAL MEDICINE · 2020 · $397,404

## 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:** 9979634
- **Project number:** 5R01DE025885-06
- **Recipient organization:** RBHS-SCHOOL OF DENTAL MEDICINE
- **Principal Investigator:** Emi Shimizu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $397,404
- **Award type:** 5
- **Project period:** 2017-06-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979634

## Citation

> US National Institutes of Health, RePORTER application 9979634, Growth factors-induced dentinogenesis (5R01DE025885-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9979634. Licensed CC0.

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