# Regulation of Skeletal progenitor cells in Osteogenesis Imperfecta

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $649,109

## Abstract

PROJECT SUMMARY
Osteogenesis Imperfecta (OI) is a congenital bone and oral-facial disorder that mainly affects bone with less well
characterized alterations in bone healing and repair. Like other skeletal diseases, at least some of the
progressive bone and craniofacial defects in OI patients have been attributed to changes in the populations and
functions of their stem/progenitor cells. In general, stem cells require a specialized environment for their
maintenance and function. Nevertheless, how normal or defective structural components of collagen regulate
skeletal stem/progenitor cells (SSPCs) is essentially unknown. Therefore, the goal of this proposal is to define
the in vivo characteristics and function of skeletal stem/progenitor cells in OI and to understand how an
abnormal OI extracellular matrix alters these stem/progenitor cells in the context of bone regeneration
and repair. We previously showed that the Mx1Cre and αSMAGFP combination can selectively label skeletal stem
cells in the periosteum and that these Mx1ÈαSMAGFPÈ periosteal cells are long-term repopulating stem cell
subsets responsible for lifelong regeneration of periosteal osteoblasts and bone repair. Moreover, our preliminary
study revealed that these periosteal SSPCs are Prx1GFP positive and selectively express KDR (VEGFR2). Human
primary periosteal cells also express KDR with multi-lineage differentiation potentials. Notably, we found that
these KDRÈ periosteal progenitor cells are significantly decreased in OI bones. Hence, we hypothesize that the
abnormal OI matrix deregulates the number and function of periosteal and bone marrow SSPCs and the OI-
associated molecular changes in stem/progenitor cells are critical for the progressive deformity and delayed or
defective healing of bones. By using a series of OI animal models and SSPC reporter mice, in which we can
differentially label periosteal and bone marrow SSPC subsets, in combination with intravital imaging and the
latest single-cell RNA-sequencing technology, we plan to pursue the following specific aims. In aim 1, we will
define the in vivo characteristics and function of periosteal and bone marrow SSPCs in clinically relevant OI
mouse models. In aim 2, we will define key OI matrix factors that regulate SSPC function and improve both
craniofacial and long bone healing. Upon completion of this work, we will achieve new biological insights into a
better understanding of the molecular and cellular mechanisms that differentially regulate SSPCs under OI
pathophysiological conditions.

## Key facts

- **NIH application ID:** 10828409
- **Project number:** 5R01DE031288-03
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Brendan Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $649,109
- **Award type:** 5
- **Project period:** 2022-07-13 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10828409

## Citation

> US National Institutes of Health, RePORTER application 10828409, Regulation of Skeletal progenitor cells in Osteogenesis Imperfecta (5R01DE031288-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10828409. Licensed CC0.

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