# Mapping temporomandibular joint (TMJ) degeneration and pain

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $589,725

## Abstract

PROJECT SUMMARY/ABSTRACT
Temporomandibular joint (TMJ) osteoarthritis (TMJOA) is a degenerative disease of the joint. It has been
challenging to manage and treat TMJOA due to our limited understanding of the molecular, cellular, and neuronal
mechanisms underlying TMJOA. The goal of this proposal is to use multi-modal single-cell and imaging
technologies to establish a high-dimensional, comprehensive molecular, cellular, and innervation map of TMJ
under healthy and OA conditions in mouse models that mimic human TMJOA. We will further validate Netrin-
1/Dcc as the potential therapeutic target of TMJOA. A major strength of this collaborative project is to integrate
the findings, skills, and distinct expertise of investigators including PI Jianfu Chen (Neuroscience), co-Is Mildred
Embree and Yang Chai (Craniofacial biology and TMJOA), collaborator Xu Cao (Neuroskeletal pain) and Hu
Zhao (TESOS volume imaging), which cannot otherwise be accomplished by the individual investigators
separately. Strong published and preliminary studies support comprehensive team of scientific approaches in
unveiling the mechanisms of TMJOA, including different TMJOA mouse models, methodology for joint pain
behavior, dynamic changes in joint pathologies and innervation during OA, 3-D imaging methods to map sensory
nerve connectome in the TMJ at micron resolution, antegrade and retrograde tracing of joint innervation,
chemogenetic functional assays of neural circuits, and single cell RNA-sequencing approaches. Importantly, our
preliminary studies have identified Netrin-1/Dcc as key mediators of TMJ cell-cell interaction and potential
therapeutic targets for mitigating TMJOA pain. These exciting preliminary data put us in a unique position to
generate the first comprehensive molecular, cellular, and innervation map of TMJ with or without OA and to
identify new therapeutic targets. Our guiding hypothesis is that TMJOA causes significant alterations in chromatin
accessibility and gene expression of disease relevant cell types including osteoclasts and synovial fibroblasts in
TMJ, which in turn cause maladaptive nociceptive innervation leading to joint pain and degeneration. To test our
hypothesis, we will: (1) create a comprehensive single-cell transcriptomic and epigenomic cell atlas for the TMJ
in TMJOA model mice and identify molecular changes that accompany TMJOA in each cell type. (2) functionally
map TMJ nociceptive innervation during OA progression. (3) validate Netrin-1/Dcc as mediators and therapeutic
targets of TMJOA pain.

## Key facts

- **NIH application ID:** 10978804
- **Project number:** 1R01DE033511-01A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Jianfu Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $589,725
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10978804

## Citation

> US National Institutes of Health, RePORTER application 10978804, Mapping temporomandibular joint (TMJ) degeneration and pain (1R01DE033511-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10978804. Licensed CC0.

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