# Mechanisms of Skeletal Stem Cell Dysfunctions in Traumatic Bone Injuries

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $297,802

## Abstract

Project Summary:
Musculoskeletal diseases and disorders represent the second leading cause of disability and are a significant
clinical burden worldwide. Among these disorders, musculoskeletal injuries can lead to complications in
approximately 10% of the cases of bone fractures, and the risk of delayed- or non-union is increased up to
46% when associated with soft tissue and vascular injuries. While muscle is thought to play an important role
in bone healing, the mechanisms of action remain poorly understood. There is a large knowledge gap in our
understanding of muscle-bone crosstalk in regulating skeletal stem cell function in bone repair. We aim to
elucidate the mechanisms by which muscle injury leads to impaired bone healing in a new muscle-bone injury
model in mice that reflects traumatic injury in human. In this model, muscle crush injury severely impacts bone
repair by delaying callus formation and stem cell recruitment. We have designed multiple experimental
approaches, based on in vitro experiments, state-of-the-art genetic tools for lineage analyses and tissue
grafting experiments in order to determine the extent to which traumatic injury in this model affects the
coordinated activation and differentiation of skeletal stem cells in bone and adjacent muscle. Through these
approaches, we will specifically identify the mechanisms of skeletal stem cell recruitment from muscle and
periosteum in the fracture callus (aim 1), characterize the impaired skeletal stem cell activation in muscle and
periosteum in the traumatic injury environment (aim 2) and the impact of traumatic injury on cartilage-to-bone
transformation during bone regeneration (aim 3). Our work will help determine the causes of non-union
associated with polytrauma and may lead to new drug- or cell-based therapies to treat traumatic
musculoskeletal injuries and delayed bone healing.

## Key facts

- **NIH application ID:** 10397641
- **Project number:** 5R01AR072707-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** CELINE I COLNOT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $297,802
- **Award type:** 5
- **Project period:** 2018-07-12 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10397641

## Citation

> US National Institutes of Health, RePORTER application 10397641, Mechanisms of Skeletal Stem Cell Dysfunctions in Traumatic Bone Injuries (5R01AR072707-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10397641. Licensed CC0.

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