# Enamel biomineralization; the role of pH cycling

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $500,880

## Abstract

PROJECT SUMMARY/ABSTRACT
Mineralized enamel is the hardest tissue in the human body, and its proper formation is critical for the protection
and maintenance of healthy teeth for a lifetime. Enamel biomineralization is directed by the epithelial derived
ameloblasts. Ameloblasts secrete enamel matrix proteins, which are then hydrolyzed and replaced by
hydroxyapatite crystals. Maturation stage ameloblasts modulate in waves to acidify approximately 80% of the
mineralizing maturation stage matrix, with the remaining approximately 20% of the matrix remaining neutral.
When pH cycling is disrupted, enamel formation is dysregulated, and the resulting enamel matrix is
hypomineralized. Though an acidic environment is unfavorable to biomineralization, matrix acidification in
enamel formation has been presumed to have a role in refinement of the hydroxyapatite (HAP) enamel crystals.
However the mechanism(s) that control pH cycling remain unclear.
In this project, we will use our novel polarized ameloblast culture system, along with Wdr72-/- and Cftr-/- mouse
models, to test our central hypothesis that ameloblasts directly regulate pH cycling in the enamel matrix, to
optimize enamel matrix mineralization. We will test this central hypothesis with the following specific aims. 1) To
determine the role of ameloblasts in acidifying the enamel matrix; 2) To determine the effects of
extracellular pH on calcium transport by ameloblasts; 3). To determine the role of matrix acidification on
protein hydrolysis and HAP crystal formation. These studies will allow us to better understand the etiology
of enamel hypomineralization, and will allow us to apply this knowledge to reduce the risk for of enamel defects.
The long-term goal of our research is to determine how pH cycling by ameloblasts directs enamel matrix
biomineralization to synthesize the unique prismatic mineralized structure that forms tooth enamel.

## Key facts

- **NIH application ID:** 10348158
- **Project number:** 5R01DE027971-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Pamela K Den Besten
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $500,880
- **Award type:** 5
- **Project period:** 2019-03-07 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10348158

## Citation

> US National Institutes of Health, RePORTER application 10348158, Enamel biomineralization; the role of pH cycling (5R01DE027971-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10348158. Licensed CC0.

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