# Cellular and molecular coordinators of large-scale bone repair

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $626,879

## Abstract

ABSTRACT
The challenge of repairing extensive bone injuries remains an unmet clinical challenge. Our research is
dedicated to exploring a novel mouse model of large-scale bone regeneration to unravel the intricate cellular and
molecular events necessary for the large-scale regeneration. While the outer periosteum and the inner
endosteum are recognized as sources of new osteoblasts during normal bone homeostasis, the precise
mechanisms governing the initiation and coordination of repair are not well-understood. We hypothesize a two-
phase repair process following large-scale injury. Initially, a sentinel-type cell population marked by the
expression of Sox9 transitions from quiescent to activated state. In the second phase, we propose that this
subpopulation orchestrates the recruitment of other cells, including bone marrow-derived subpopulations, and
culminating in a callus spanning the injury site. Building on our previous work, which has shown the requirement
for Sox9-lineage cells in large-scale repair, in Aim 1 we investigate the mechanisms that trigger activation of
these cells in response to injury. Specifically we test that the gene Fos is required for their activation and for the
transcription of genes important for coordinating repair. In Aim 2 we determine if these Sox9-lineage cells recruit
bone marrow stromal cells expressing Cxcl12, with this interaction being vital for robust bone callus generation.
Finally, In Aim 3, we determine if Sox9-lineage cells originating from the rib possess distinctive features that
enable them to facilitate the healing of critical-sized femur injuries, possibly through recruiting Cxcl12-lineage
cells from the femur bone-marrow niche. The successful completion of these experiments will provide invaluable
insights into the critical cell types and mechanisms driving large-scale repair in a mammalian model. These
insights could lay the groundwork for future pre-clinical studies targeting challenging skeletal injuries in patients.

## Key facts

- **NIH application ID:** 10982004
- **Project number:** 1R01AR083445-01A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Francesca V Mariani
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $626,879
- **Award type:** 1
- **Project period:** 2024-08-16 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10982004

## Citation

> US National Institutes of Health, RePORTER application 10982004, Cellular and molecular coordinators of large-scale bone repair (1R01AR083445-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10982004. Licensed CC0.

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