# Defining the unique capacity of the miniature joint model for investigating the role of adipose tissue and its impacts on osteoarthritis

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $711,760

## Abstract

Abstract: Osteoarthritis (OA) is the most prevalent form of arthritis and results in reduced mobility and pain.
Epidemiological and clinical data have shown a correlation between OA and specific risk factors like obesity.
Particularly, overweight humans have a 4-5× increased risk of knee OA. Currently, the association is not fully
understood, and there are no FDA-approved drugs that can cure obesity-associated OA. For decades, animals,
particularly rodents, have been the most commonly used disease models that provided invaluable insights into
OA pathogenesis. However, one animal model is unlikely to simulate all OA phenotypes in humans. Furthermore,
a low rate of successful translation from current OA animal models to clinical trials was reported. A
complementary model that uses human cells and enables tissue crosstalk simulating human physiology would
thus be a valuable tool for recapitulating specific features of human OA that cannot be modeled in animals.
Recently, our team has engineered an in vitro microphysiological joint chip (miniJoint) that integrates the
osteochondral, synovial, and adipose analogs with immune cell (macrophage) components. In this new project,
we will continue the development and application of the miniJoint by introducing “obese” adipose tissues and
mechanical loading mechanisms to determine whether this novel in vitro system can be used to investigate how
non-obese and obese adipose tissues interact with other tissues during OA pathogenesis. The hypothesis of the
proposed studies is that “normal” adipose tissue drives cartilage degradation in response to interleukin-1β or
mechanical injuries, whereas “obese” adipose tissue secretes detrimental by-products causing cartilage
degradation and synovial inflammation, which is further exacerbated by interleukin-1β treatment or excessive
mechanical loading. The hypothesis will be tested by performing the following three specific aims. In Aim 1, we
will define the influence of normal adipose tissue in the pathogenesis of OA in the miniJoint. Specifically, we will
use interleukin-1β or an in-house developed unit to introduce injuries to the miniJoint. In Aim 2, we will develop
an “obese” fat model in the miniJoint and examine if the by-products from dysfunctional adipose tissue in the
miniJoint will result in inflammation in the synovial tissue and the degradation of cartilage. We expect that
increasing mechanical loading will lead to significant cartilage degradation when the cartilage is simultaneously
exposed to the by-products from “obese” adipose tissue. In Aim 3, we will conduct comprehensive comparisons
among cartilage samples from the miniJoint, animal models, and human donors to define the unique capacity of
the miniJoint to accurately model human OA. The success of the proposed studies will define critical aspects of
human OA that can be readily modeled in the miniJoint. Through complementary studies in the miniJoint and
animal models, the mechanistic basis of obese a...

## Key facts

- **NIH application ID:** 10802822
- **Project number:** 1R01AR082386-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Bruce A. Bunnell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $711,760
- **Award type:** 1
- **Project period:** 2024-05-15 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802822

## Citation

> US National Institutes of Health, RePORTER application 10802822, Defining the unique capacity of the miniature joint model for investigating the role of adipose tissue and its impacts on osteoarthritis (1R01AR082386-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10802822. Licensed CC0.

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