# Viscoelastic Properties of Normal and OA Chondrons

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $494,365

## Abstract

PROJECT SUMMARY / ABSTRACT
Osteoarthritis (OA) is a highly prevalent, disabling degenerative disease of the joints that is characterized by
progressive deleterious changes in the articular cartilage, subchondral bone, and other joint tissues. This
project will exploit emerging evidence from exome sequencing in a unique selection of (early onset) familial OA
cases that resulted in the identification of high impact mutations in COL6A3 likely causal to OA. The
mechanism by which such a mutation increases the risk for OA is unclear, partly because there is substantial
genetic variation among the population and lifestyle differences that can affect the development of OA. We
propose to develop a novel in vitro system for studying the functional effect of identified OA causal variants on
the biochemical and mechanical properties of articular cartilage using genome editing of COL6A3 in induced
pluripotent stem cells (iPSCs) and cartilage tissue engineering. Type VI collagen plays a critical role in the
function of the chondron – the chondrocyte and its surrounding pericellular matrix – which has been shown the
regulate the biological and biomechanical environment of chondrocytes in articular cartilage. We will use a
combined experimental and theoretical modeling approach to determine how changes in the physicochemical
properties of the PCM with COL6A3 mutation influence the mechanical interactions between the chondrocyte
and ECM in chondrogenically differentiated iPSCs. We will examine the early signaling events as well as the
long-term influence of COL6A3 knockout or mutation on chondrocyte response to loading. Finally, we will
examine the effect of the COL6A3 knockout or mutation on the epigenetically controlled changes of the
transcriptome of chondrocytes in response to loading. A detailed understanding of these mechanisms will
provide critical insight into the development of new pharmacologic, regenerative, or physical therapies for OA.

## Key facts

- **NIH application ID:** 10375575
- **Project number:** 5R01AG015768-24
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Farshid Guilak
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $494,365
- **Award type:** 5
- **Project period:** 1998-01-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375575

## Citation

> US National Institutes of Health, RePORTER application 10375575, Viscoelastic Properties of Normal and OA Chondrons (5R01AG015768-24). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10375575. Licensed CC0.

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