# Investigating injury response and bone regeneration in Down syndrome mouse models

> **NIH NIH F31** · TEXAS A&M UNIVERSITY · 2022 · $37,300

## Abstract

Project Summary/Abstract
Down Syndrome (DS) is a common birth defect caused by trisomy of human chromosome 21 (Hsa21). DS leads
to a vast array of clinical abnormalities affecting most systems of the body, including delayed wound healing, and
an increased risk of long bone and vertebral fractures. Previously, this laboratory has shown that DS patients
have low bone turnover leading to decreased bone mineral density and delayed accrual of peak adult bone
mass, and also confirmed the low bone mass phenotype in mouse models of DS. Additionally, it has been
recently reported that COX2/PGE2 expression is impaired in DS human dermal fibroblasts, which could
contribute to the delayed wound healing and increased risk of infections in the DS population. PGE2 and its
receptors are major mediators of inflammation, wound healing, bone formation and bone healing. More
specifically, the PGE2 receptor subunit 2 (EP2, Ptger2) and EP4, have been shown to regulate bone formation,
and play a crucial role in fracture healing, whereas EP3 and EP4 contribute to macrophage recruitment, the
immune response, and lymphangiogenesis in wound healing. However, what is not known is how PGE2
signaling contributes to bone repair and whether low bone accrual in DS impacts bone regeneration. The
overarching objective of this proposal is to characterize bone healing in DS mouse models and determine if
pharmaceutical treatment at different stages during the regenerative process is able to enhance regeneration in
DS. This project will test the hypothesis that bone healing is significantly impaired in DS, and that decreased
bone turnover leads to attenuated bone regeneration. This study will utilize the DS mouse models, Dp16 and
Ts65Dn, that demonstrate the low bone mass phenotype consistent with the low bone mass observed in DS
patients, to investigate de novo bone regeneration after amputation of the terminal phalanx (P3). P3 amputation
is a model of mammalian injury that faithfully triggers a well-defined regenerative sequence of events that initiates
with inflammation followed by bone resorption, wound closure, and de novo bone formation, allowing the
characterization of the entire injury response. Experiments in Aim 1 will seek to characterize P3 regeneration in
the DS mouse models compared to WT littermates to test the hypothesis that bone regeneration is impaired in
DS mouse models. Aim 2 will investigate the early, or lytic, phase of regeneration and determine whether
treatment with a PGE2 receptor (EP3 and EP4) agonist elicits an immune and wound healing response that is
sufficient to enhance regeneration in DS. The proposed studies of de novo bone regeneration will help to close
the gap in knowledge regarding how DS impacts bone healing and repair, and provide insight into how patient
care can be modified to adequately treat bone injuries in the at-risk DS population.

## Key facts

- **NIH application ID:** 10534436
- **Project number:** 1F31HD110287-01
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** Kirby M. Sherman
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $37,300
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10534436

## Citation

> US National Institutes of Health, RePORTER application 10534436, Investigating injury response and bone regeneration in Down syndrome mouse models (1F31HD110287-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10534436. Licensed CC0.

---

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