# Testing Miniature Knee Joint System as a New Tool to Study Neuroimmune Interactions in Osteoarthritis Pain

> **NIH NIH F31** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $48,974

## Abstract

PROJECT SUMMARY
Osteoarthritis (OA) is a painful and debilitating disease, in which pain is the primary symptom that prompts
patients to seek medical care. Currently, there are not any safe and effective treatments for OA and associated
pain that have reached FDA approval. The association between pain and OA is not well understood, and
radiographic images do not correlate with pain severity. I propose to use a novel microphysiological system
equipped with cartilage tissue, synovial-like tissue with fibroblasts, and macrophages that are innervated with
human neurites to study acute pain associated with neuro-immune interactions that occur during OA. I
hypothesize that a positive feedback loop between neuro-immune interactions contributes to the ongoing pain
and hypersensitivity associated with OA.
To test this hypothesis, I will use our novel microphysiological system to first understand the influence of synovial-
like tissue inflammatory molecules on innervating neurons through the treatment of human DRG with different
conditioned mediums from OA-like cartilage tissue and inflamed synovial-like tissue. I will then investigate the
role of chemokines on nociception, with a focus on chemokine CXCL-1 through a series of experiments such as
the exogenous treatment of CXCL-1 and assessment of conditioned medium through proteomics. Second, I will
assess the role of neuropeptides SP and CGRP on synovial immune cells. I will begin by assessing the
contribution of macrophages to inflammatory output in the synovial-like tissue. Then I will use exogenous
treatments of SP and CGRP and innervation to specify mechanisms of inflammation promoted by these
neuropeptides. This proposed work will broadly apply to OA pain, mediating therapeutic targets and mechanisms
behind synovial-related acute OA pain. Lastly, it can be used to model other musculoskeletal diseases, such as
pain in intervertebral disc degeneration. This proposal highlights the contributions made by the PI throughout the
training, which will primarily focus on the assessment of chemokines on nociception and how neuropeptides
affect immune cells in the synovial-like tissue. Successful completion of this proposal is the critical step to
providing a platform for understanding neuro-immune interactions, testing pain-mediating therapeutics on human
tissue, and developing disease-modifying osteoarthritis drugs.

## Key facts

- **NIH application ID:** 10995713
- **Project number:** 1F31AR083814-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Meagan Joanne Makarczyk
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10995713

## Citation

> US National Institutes of Health, RePORTER application 10995713, Testing Miniature Knee Joint System as a New Tool to Study Neuroimmune Interactions in Osteoarthritis Pain (1F31AR083814-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10995713. Licensed CC0.

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