# WNT1 Function in Stem Cells in Osteogenesis Imperfecta and Craniofacial-Skeletal Tissues

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $576,000

## Abstract

PROJECT SUMMARY
Skeletal stem cells (SSCs) are necessary for the homeostasis and repair of bone and cartilage. In craniofacial
bones, periosteal skeletal stem/progenitor cells (P-SSCs) and suture mesenchymal cells play a critical role in
bone homeostasis and regeneration. However, due to the restricted distribution and lack of specific markers,
little is known about the function of craniofacial P-SSCs and about their specific regulatory mechanisms in
homeostasis and response to bone injury. Patients with Osteogenesis Imperfecta (OI) have dysregulation of
craniofacial and skeletal bone homeostasis. WNT1 mutations cause recessive OI and early onset
osteoporosis and our preliminary data support altered craniofacial stem cell function. Therefore, the main
objective of this research proposal is to define the in vivo characteristics and unique regulatory mechanisms of
craniofacial P-SSCs, and to test if Wnt1 and α-sclerostin antibody augmentation of Wnt signaling in general are
critical for these P-SSCs' response to bone injury. We hypothesize that craniofacial P-SSCs have unique
molecular characteristics compared to long bone P-SSCs and that the regulation of these P-SSCs by Wnt1 is
critical for craniofacial bone homeostasis, regeneration and repair. In combination with previously known SSC
markers, we have newly identified selective markers for P-SSCs that enables us to isolate highly purified
mouse P-SSCs and to analyze their gene expression profiles and to test their bone forming ability by
transplantation of these P-SSCs into calvarial defects. We thus propose to answer the below questions in
achieving the specific aims: Specific Aim 1: What are unique characteristics and function of craniofacial P-
SSCs compared to long-bone P-SSCs. Specific Aim 2: How does Wnt1 signaling regulate the maintenance
and function of craniofacial P-SSCs? Specific Aim 3: What are the functional consequences of loss or gain of
Wnt1, and α-sclerostin therapy on craniofacial bone regeneration? These studies will identify factors that
regulate the specification of SSC from different calvarial and long bone sources and the contribution of Wnt1
and effects of α-Sost treatment in regulating bone formation, and the proliferation, migration, and differentiation
of neural crest derived-sutural vs. periosteal SSCs in homeostasis and repair.

## Key facts

- **NIH application ID:** 10316864
- **Project number:** 1R01DE031162-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Brendan Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $576,000
- **Award type:** 1
- **Project period:** 2021-09-10 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10316864

## Citation

> US National Institutes of Health, RePORTER application 10316864, WNT1 Function in Stem Cells in Osteogenesis Imperfecta and Craniofacial-Skeletal Tissues (1R01DE031162-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10316864. Licensed CC0.

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