# FIBRONECTIN AND CARTILAGE DESTRUCTION IN OSTEOARTHRITIS

> **NIH NIH R01** · CORNELL UNIVERSITY · 1992 · $173,278

## Abstract

Our long-term objective is to document changes associated with the early
stage of osteoarthritis (OA) in dogs and to identify factors that modify
the disease.  This proposal has two main and related objectives:  1) to
identify the role of fibronectin in cartilage, and 2) to identify
factors biochemical or mechanical, which influence fibronectin
biosynthesis in cartilage and promote increased production of this
biding protein by chondrocytes in the degenerative cartilage of
individuals with incipient or obvious OA.

Our specific aims are:  1) To characterize a recently identified matrix
proteoglycan which binds tightly to fibronectin in cartilage, and to
define at the molecular level, those structural characteristics of
cartilage fibronectin which make it distinct from plasma or synovial
fluid fibronectin.  This information would permit us to clarify the
mechanisms by which fibronectin binding is involved in matrix
organizational and function.  2) To establish that chondrocytes in OA
cartilage in vivo differ from normal cells because they synthesize
increased amounts of fibronectin.  We would use available cDNA as a
probe for increased mRNA for fibronectin and also use new methods of
flow cytometry to characterize chondrocytes shape, increased mitotic
activity, and receptors for fibronectin.  This would constitute strong
evidence that increased synthesis by the chondrocyte is a major factor
in fibronectin accumulation in OA cartilage.  3) To culture cartilage
for up to two weeks in a defined media, supplemented with insulin and
calcium sufficient to maintain optimal levels of proteoglycan synthesis;
to determine rates of collagen and fibronectin synthesis under these
conditions and to use addition of factors such as TGF-B, interleukin-1
or the application of precisely defined cyclic and static compressive
forces on cartilage explants in defined media to induce increased
fibronectin accumulation in conjunction with proteoglycan loss.  this
would permit us to mimic, in vitro, two well known characteristics of
degenerating cartilage in OA joints.

The proposed experiments are designed to test the hypothesis that
fibronectin has a purposeful role in cartilage homeostasis and that
increased levels of fibronectin in the degenerative cartilage reflect a
perturbation in chondrocyte function and result in disruption of matrix
assembly and cartilage destruction in OA.

## Key facts

- **NIH application ID:** 3157334
- **Project number:** 5R01AR035664-07
- **Recipient organization:** CORNELL UNIVERSITY
- **SAM.gov UEI:** G56PUALJ3KT5
- **Principal Investigator:** GEORGE LUST
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $173,278
- **Award type:** 5
- **Project period:** 1986-09-01 → 1994-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3157334

## Citation

> US National Institutes of Health, RePORTER application 3157334, FIBRONECTIN AND CARTILAGE DESTRUCTION IN OSTEOARTHRITIS (5R01AR035664-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3157334. Licensed CC0.

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