# REGULATION OF GENE EXPRESSION IN CARTILAGE

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 1993 · $174,322

## Abstract

In osteoarthritis, the major and central changes occur in the hyaline
cartilage.  Remodeling and repair of the joint structure often accompany the
progression of disease and the ability of cartilage to repair has been
questioned.  To provide a basis for comparison to the pathological
situation, it is necessary to define the basic mechanisms that regulate
expression of a specific extracellular matrix.  It is proposed that
cartilage chondrocytes respond to environmental factors by synthesizing
specific products which may or may not contribute to maintenance of proper
matrix architecture and function.  This will be investigated by continued
studies defining the influence of specific factors such as IGF-I and TGF-B
(positive modulators of type II collagen synthesis) and IL-1 and gamma
interferon (negative modulators) on biosynthesis of the predominant classes
of cartilage matrix molecules (collagen, proteoglycans and link proteins)
and the mechanisms through which they act.  Specific questions asked will
be:  is the matrix phenotype coordinately regulated?  How do factors
potentially in the environment of the chondrocyte such as cytokines and
immune mediators affect the expression of the appropriate phenotype?  and
what factors are necessary to promote synthesis of the proper phenotype?  A
model system has been developed and characterized in which bovine articular
chondrocytes in high density monolayer culture can be used to determine the
biosynthetic capability of the cells.  The methodologies of molecular
biology and biochemistry will be used to investigate gene expression in
adult articular chondrocytes.  Large aggregating proteoglycans, small
proteoglycan, type II collagen and link proteins will be measured.
Eventually, the response of adult tissue will be compared to that of fetal
and calf cartilage.  In addition, detailed analyses will be undertaken on
the mechanism of regulation of type II collagen gene transcription and
biosynthesis of multiple link proteins.  These findings may be extremely
significant to the concept of cartilage as an anlage to bone, in "aging"
joint cartilage and in diseases or injured cartilage.

## Key facts

- **NIH application ID:** 3157859
- **Project number:** 5R01AR036994-07
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **SAM.gov UEI:** HD1WMN6945W6
- **Principal Investigator:** LINDA J SANDELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $174,322
- **Award type:** 5
- **Project period:** 1987-01-01 → 1994-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3157859

## Citation

> US National Institutes of Health, RePORTER application 3157859, REGULATION OF GENE EXPRESSION IN CARTILAGE (5R01AR036994-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3157859. Licensed CC0.

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