# Delaware Center for Musculoskeletal Research

> **NIH NIH P20** · UNIVERSITY OF DELAWARE · 2024 · $502,654

## Abstract

PROJECT SUMMARY
Inflammation is a major driver of disorders such as temporomandibular joint osteoarthritis (TMJ-OA) has been
implicated in a significant cohort of patients with temporomandibular disorders (TMDs), a collective group of
conditions that can lead to debilitating pain, persistent headaches, and impaired range-of-motion. Recent clinical
and animal studies suggest that inflammation can perpetuate further TMJ harm, sprouting of sensory axons
innervating the joint, and altered excitability of sensory neurons resulting in the formation of chronic neuropathic
pain. Further, OA’s wide-ranging etiologies are further complicated by understudied sexually dimorphic
elements that increase the risk of joint degeneration and hypersensitivity to pain in women. Thus, there is an
urgent need for comprehensive evaluation of TMJ and innervating sensory neurons across sex in OA to
determine the mechanisms that underlie sensory and neuropathic OA pain, and the associated sexual
dimorphisms create significant barriers for developing targeted, mechanism-specific therapies for OA and OA
pain. To fill this knowledge gap, we propose a team science proposal that will take a multidisciplinary and
multi-omics approach. Taking advantage of the team’s complementary expertise in OA mouse models, single-
cell transcriptomics, and musculoskeletal biology (Lim; Co-PL#1) and neural tracers, single-cell spatial
proteomics, and neurobiology (Keeler; Co-PI#2), our objective is to use a multi-omic approach to identify novel
target cell populations and molecular mechanisms that drive sexually dimorphic TMJ-OA pathophysiology.
Ultimately, the imaging mass cytometry-based proteomic analysis of the sensory neurons that innervate joint-
associate tissues will enhance our understanding of how chronic exposure to inflammatory and degenerative
conditions, such as those observed in patients with osteoarthritis, impact the nature and functionality of joint-
innervation neurons. In addition, understanding which transcriptomic alterations translate into changes at the
protein-level will help us identify general and sex-specific therapeutic candidates to treat chronic joint pain.
Alignment with the Parent Project: These cutting-edge molecular profiling technologies are distinct, yet highly
complementary to the research aims proposed in the parent grant (P20GM139760; Delaware Center for
Musculoskeletal Research). Future plans: We are excited to have the opportunity to build collaboration among
two labs and obtain key pilot data. The completion of the supplement will lead to a larger co-PI R01 project that
will determine the molecular and cellular mechanisms that drive chronic and neuropathic pain in TMJ-OA. We
will leverage the resources and expertise through the parent COBRE and the existing INBRE at UD.

## Key facts

- **NIH application ID:** 11045553
- **Project number:** 3P20GM139760-04S2
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** DAWN M ELLIOTT
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $502,654
- **Award type:** 3
- **Project period:** 2021-02-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11045553

## Citation

> US National Institutes of Health, RePORTER application 11045553, Delaware Center for Musculoskeletal Research (3P20GM139760-04S2). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11045553. Licensed CC0.

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