# Role and regulation of PRX1 expressing cells during calvarial bone regeneration

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $16,166

## Abstract

Craniofacial surgeons and neurosurgeons perform numerous bone regeneration procedures to treat calvarial
congenital abnormalities or lesions due to trauma and cancer. Current procedures require therapeutic aids to
foster bone regeneration, as healing of calvarial bone defects often results in fibrous non-unions unable to protect
the brain from injuries. Unfortunately, the available therapeutic aids based on recombinant growth factors present
with severe limitations in terms of efficacy and safety. Ex vivo manipulation and expansion of skeletal stem cells
has also been proposed as an alternative to the growth-factor based therapies. However, these cell-based
regenerative strategies have shown variability of the regenerative outcomes. Therefore, more effective bone
regenerative strategies for craniofacial defects are critically needed.
We have recently shown that PRX1 is a marker of stem cells residing in the sutures of the mouse calvaria.
Postnatal PRX1 expressing cells (pnPRX1+ cells) reside exclusively within the calvarial sutures, are required for
regeneration of calvarial bone defects, and decline in number with age. Our current data further indicates that
pnPRX1+ cells respond to activation of Wnt signaling by differentiating into osteoblasts and to inhibition of Wnt
signaling by proliferating. With these findings and with the goal of developing clinically viable alternatives to the
current calvarial bone regeneration therapies, in Aim 1 we propose to study the Wnt-regulated cellular
mechanisms that control the migration of pnPRX1+ cells from the suture niche to a calvarial bone defect located
remotely from the suture. In Aim 2 we propose to test the ability of Wnt inhibitor small molecules or of small
fragments of transplanted sutures to induce regeneration of calvarial bone defects.
By understanding the molecular mechanisms that govern the contribution of the stem cells of the suture to the
regeneration of a calvarial bone defect and by defining novel strategies to harness these stem cells within their
niches, our studies may lead to the development of novel therapies for calvarial bone regeneration, helping
craniofacial surgeons and neurosurgeons with their need to regenerate a part of the skeleton so vital for
protection of the brain.

## Key facts

- **NIH application ID:** 10329059
- **Project number:** 3R01DE026155-02S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Giuseppe Intini
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $16,166
- **Award type:** 3
- **Project period:** 2021-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10329059

## Citation

> US National Institutes of Health, RePORTER application 10329059, Role and regulation of PRX1 expressing cells during calvarial bone regeneration (3R01DE026155-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10329059. Licensed CC0.

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