# Mapping the joint-nerve interactome of the knee

> **NIH NIH UC2** · RUSH UNIVERSITY MEDICAL CENTER · 2023 · $1,223,463

## Abstract

ABSTRACT
This supplement addresses are proposed studies are in the context of spine tissue damage and chronic low
back pain (LBP). The goals of the parent grant are to construct 3D models of the sensory innervation of the knee,
compose a cell atlas in which knee afferents are transcriptionally profiled at a single cell resolution, and document
the nerve-joint cell interactome at the transcriptional level.
The supplement substantially expands the scope and potential impact of the parent program by examining
mechanisms of intervertebral disc (IVD) degeneration (IDD), facet joint (FJ) osteoarthritis (OA) and the
interaction of these tissues with neurons in the generation of low back pain. The inclusion of the FJ also extends
the portfolio of joints (knee and temporomandibular joints) that are currently being investigated in the RE-JOIN
consortium.
The team includes investigators at Rush University (PI Dr. Anne-Marie Malfait) and Scripps Research (PI Dr.
Martin Lotz) in the funded UC2 project for the analysis of knee joints and adds new methods for the analysis of
IVD and FC degeneration and the team at the University of Texas, Dallas (PI Dr. Theodore Price) adds expertise
in the analysis of dorsal root ganglia (DRG). The team at Scripps has a long-standing program on mechanisms
of knee OA and performed prior work on mechanisms of IDD, using mouse models and human spines. Omics
analyses were applied to define cell populations and their gene regulatory networks in healthy and degenerated
IVD. The team at Rush is a leader in the analysis of pain mechanisms in OA and has expertise in the analysis
of neural structures in knee joints and in the analysis of chronic pain mechanisms. The two teams are working
together in the funded RE-JOIN project about knee pain. Our unique approach is to examine spine and knee
tissues from the same young healthy and older donors with OA and IDD for innervation, transcriptome and
epigenome at tissue, single cell, and spatial levels. The integrative analysis of neural and connective tissue
changes during IDD will reveal critical interactions that promote tissue damage and pain.

## Key facts

- **NIH application ID:** 10861323
- **Project number:** 3UC2AR082186-01S1
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Martin K Lotz
- **Activity code:** UC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,223,463
- **Award type:** 3
- **Project period:** 2023-09-13 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10861323

## Citation

> US National Institutes of Health, RePORTER application 10861323, Mapping the joint-nerve interactome of the knee (3UC2AR082186-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10861323. Licensed CC0.

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