# Sensory nerve regulation of growth plate repair

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2024 · $216,150

## Abstract

Project Summary
Injuries of the growth plate account for nearly 20% of all fractures in children and often result in impaired bone
growth. Once damaged, cartilage tissue of the growth plate is often replaced by unwanted bone tissue. This
“bony bar” can cause angular deformities of the bone or stunt longitudinal bone growth. Angiogenesis is
known to precede bony bar formation after growth plate injury, yet the mechanistic underpinnings of this (and
by extension the means to prevent it) are poorly understood.
Recent studies from our laboratory have demonstrated an essential role for skeletal sensory nerves in the
regulation of skeletal cells and tissues. Most skeletal neurons are NGF (Nerve growth factor) responsive TrkA
(Tropomyosin receptor kinase A) fibers, which our group has shown to interact with skeletal tissues to
influence skeletal development and repair. Most recently, we reported that TrkA+ neurons regulate vascular
proliferation and angiogenesis. This work has led us to the entirely new hypothesis that skeletal sensory
neurons may regulate response to growth plate injury, potentially via regulation of angiogenesis, and that this
could be targeted therapeutically. To assess this hypothesis, our studies are divided into two Specific Aims:
Specific Aim 1. Identify molecular determinants of sensory neural regulation of growth plate injury
response. We will utilize multi-tissue single cell RNA sequencing (scRNA-Seq) to map the neuroskeletal
interactions after growth plate injury. Analysis of both the injured physis and neural soma in the corresponding
lumbar dorsal root ganglia (DRG) neurons will recreate the neuro-skeletal interactome before and after injury.
Next, experiments will be performed within TrkAF592A transgenic animals, in which injury site innervation and
bony bar formation are attenuated. Our Aim 1 hypotheses are that: (1) chemical-genetic neuronal inhibition
may disrupt pathologic bony bar formation, and growth plate angiogenesis, and (2) single cell sequencing will
map the neuro-skeletal interactome and predict neural regulatory mechanisms.
Specific Aim 2. Target sensory neurons via a small molecule inhibitor to prevent growth plate
innervation and bony bar formation. In Aim 2, we will utilize a small molecule inhibitor of TrkA (AR786) in
order to pharmacologically target TrkA signaling so as to inhibit growth plate injury site innervation, vascularity
and bony bar formation. Studies will be performed in Thy1-YFP reporter animals which permit visualization of
nerve ingrowth during growth plate repair. Our Aim 2 hypothesis is that small molecule TrkA inhibition during
growth plate injury will prevent injury site innervation and pathologic bony bar formation.

## Key facts

- **NIH application ID:** 10894337
- **Project number:** 1R21AR083544-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** AARON W JAMES
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $216,150
- **Award type:** 1
- **Project period:** 2024-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894337

## Citation

> US National Institutes of Health, RePORTER application 10894337, Sensory nerve regulation of growth plate repair (1R21AR083544-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10894337. Licensed CC0.

---

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