# Molecular Signaling in Dentinogenesis and Dental Caries Risk

> **NIH NIH R03** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $296,734

## Abstract

ABSTRACT
Dental Caries is one of the most common chronic diseases worldwide, and one of the most understudied
conditions in patients with rare diseases, critically undervalued in healthcare. The high prevalence of dental
caries emphasizes the imperative need for studies focused on understanding host susceptibility, to deliver more
efficient prevention strategies tailored to each individual. Over the last decade, human genetic studies have
made significant progress in identifying genetic risk factors associated with dental caries susceptibility,
occurrence, and progression. Nevertheless, there is no follow-up on genome-wide association studies (GWAS)
that identified dental caries risk genes, including those coding for transcription factors as dental caries risk loci.
Recently, the candidate’s research has demonstrated that deficiency of the mineralization-regulating
transcription factor Trps1 in odontoblasts —the cells that form dentin—compromises the quality of dental tissues
and increases susceptibility to dental caries. However, further studies are required to elucidate the role of Trps1
in dentinogenesis and its effect on enamel, to explain the higher predisposition of these tissues to acid-induced
demineralization. This project builds upon the clinical findings of the increased susceptibility of dental caries in
patients with heterozygous mutations in the TRPS1 gene coding for the TRPS1 transcription factor (OMIM
190350). The specific aims of this proposal are to (i) determine the mechanism whereby Trps1 regulates
communication between developing odontoblasts/ameloblasts and the formation of mantle dentin, as well as to
(ii) identify genes and cellular processes dysregulated in the tooth due to Trps1 deficiency in odontoblasts. The
experimental design employs Trps1 conditional knockout mice and uses advanced methodology to assess
mineralized dental tissues and global changes of gene expression in dentin and enamel-forming cells.
Specifically, we will (i) determine the effect of Trps1 on the micro- and nanomorphology of dentin and enamel
including dentino-enamel junction, (ii) assess the role of Trps1 in formation of mantle dentin (essential to support
the overlying enamel layer), (iii) assess whether Trps1 regulates the Wnt signaling pathway implicated in
molecular communication between developing odontoblasts/ameloblasts and (iv) determine consequences of
odontoblast- specific Trps1 deficiency on global changes of gene expression in ameloblasts and odontoblasts.
This proposal constitutes a proof-of-concept of the importance of transcription factors in susceptibility to dental
caries. A fundamental understanding of the transcriptional regulation of the formation and mineralization of dental
tissues, as well as the crosstalk between odontoblasts/ameloblasts, will result in opportunities to develop better
options for prevention of dental caries and for the identification of high-risk groups with developmental defects
of dental tissues. The resu...

## Key facts

- **NIH application ID:** 11038662
- **Project number:** 1R03DE034501-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Mairobys Socorro
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $296,734
- **Award type:** 1
- **Project period:** 2024-09-19 → 2026-09-18

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11038662

## Citation

> US National Institutes of Health, RePORTER application 11038662, Molecular Signaling in Dentinogenesis and Dental Caries Risk (1R03DE034501-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11038662. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*