# Characterization of sodium dependent phosphate transporter 2 signaling in hard tissue mineralization

> **NIH NIH F30** · UNIVERSITY OF WASHINGTON · 2024 · $49,374

## Abstract

Project Summary
Growth and homeostasis of bones require calcium and inorganic phosphorus (Pi). With millions of Americans
suffering from bone mineralization disorders, there exists a need for understanding processes governing hard
tissue mineralization. Pi is implicated in not only forming hydroxyapatite, the main crystal giving bone its
compressive strength, but also regulating osteoblast and chondrocyte differentiation and function. PiT-2 (gene:
Slc20a2) is the major form of sodium-dependent Pi transporters in mineralized tissue. Our laboratory is one of
the first to have identified its potent role in regulating skeleton development and mineralization. Knockout of the
PiT-2 gene in mice resulted in tooth and bone mineralization abnormalities, as evidenced by reduced osteoblast
numbers, bone density and volume, and impaired incisor development and amelogenesis. The focus of this
research is to explore further the role of PiT-2 in cellular and extracellular processes governing skeletogenesis,
dentinogenesis, and amelogenesis. Specifically, Aim 1 will confirm and extend our preliminary findings to
determine whether PiT-2 is required for regulation of odontoblast and ameloblast numbers, differentiation, and/or
mineralizing activity with deficiencies leading to impaired dentinogenesis and amelogenesis. A role of PiT-2 in
dentin repair and tertiary dentin formation will also be studied using a molar injury mouse model. In Specific Aim
2, we will define the mechanisms of action of PiT-2 in mineralizing cells using osteoblasts as an example. A Pi
transport and sensing/signaling function of PiT-2 will be dissected through engineered PiT-2 transport deficient
mutants. We expect these studies to provide a better understanding of how Pi influences functions of hard tissue
forming cells, serving as a basis to develop novel therapeutics for patients suffering from mineralization
disorders, such as osteoporosis and osteopenia. This project will take place at the University of Washington with
collaborations between the Departments of Bioengineering and Oral Health Sciences during DDS-PhD training
of the PI. The PI will develop critical thinking skills, learn state-of-the-art cellular and molecular techniques, in
vivo transgenic mouse models, and data analysis that will prepare him for independent research. Ultimately, a
strong mentorship team, multidisciplinary collaborative effort, and resources at the University of Washington with
support through this award will prepare the trainee for a future tenure-track faculty position to study
biomineralization processes.

## Key facts

- **NIH application ID:** 10845705
- **Project number:** 5F30DE029094-06
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Philip Adam Walczak
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $49,374
- **Award type:** 5
- **Project period:** 2019-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10845705

## Citation

> US National Institutes of Health, RePORTER application 10845705, Characterization of sodium dependent phosphate transporter 2 signaling in hard tissue mineralization (5F30DE029094-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10845705. Licensed CC0.

---

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