# COLLAGEN GENE EXPRESSION IN CHONDROCYTES IN INFLAMMATION

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 1988 · $113,329

## Abstract

Chondrocytes are capable of participating in breakdown of their own
matrix in response to inflammatory mediators and in repair of the
damaged collagen network.  A cell culture model has been
established employing human chondrocytes in monolayer culture as
target cells for the effects of potential intercellular mediators
produced by inflammatory cells which might modulate chondrocyte
functions such as synthesis of a cartilage matrix macromolecules.
We found that one inflammatory mediator, IFN-gamma, a product of
T-lymphocytes, suppresses synthesis of type II collagen as well as
types I and III collagens and fibronectin and levels of cellular
procollagen mRNAs in chondrocytes.  Interleukin 1 (IL-1), a
monocyte product which stimulates the synthesis of PGE2 and neutral
proteases, increases synthesis of types I and III collagens and
associated procollagen mRNA levels when the synthesis of PGE2 which
inhibits collagen synthesis, is blocked by indomethacin.  In
contrast, IL-1 suppresses levels of type II and type IX procollagen
mRNAs thereby inducing loss of cartilage-specific phenotype.  The
aim of this proposal is to determine how these positive and
negative signals control collagen gene expression.  Preliminary
evidence indicates that some of these effects are modulated at the
transcriptional level.  Using recombinant preparations of IL-1 and
IFN- gamma and cultured human chondrocytes as well as other human
tissue cells and mouse cells as targets, control of collagen gene
expression will be studied by:  (1) assays of nuclear transcription
in vitro and stability in cellulo of procollagen mRNAs; (2) DNAase
I hypersensitivity and S1 nuclease protection experiments using DNA
probes containing promoter and enhancer sequences of collagen
genes; (3) analysis of cis-acting elements by transient
transfection experiments using fusion construct of 5'flanking DNA
(promoter + enhancer regions of different collagen genes coupled
to a reporter gene such as chloramphenicol acetyl transferase
(CAT); (4) analysis of potential trans-acting factors by DNA-
protein gel mobility shift assay and/or DNA footprinting
techniques.  Since IL-1 has opposite effects on type II vs type I
and type III collagen gene expression, a major goal will be to
determine whether similar or different trans-acting factors and/or
cis-acting elements are involved.  These inflammatory mediators may
induce inappropriate repair of cartilage matrix in vivo and these
studies should determine whether their effects are mediated
primarily at the transcriptional or post-transcriptional level.

## Key facts

- **NIH application ID:** 3156822
- **Project number:** 2R01AR034390-04A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **SAM.gov UEI:** FLJ7DQKLL226
- **Principal Investigator:** MARY B GOLDRING
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $113,329
- **Award type:** 2
- **Project period:** 1984-08-01 → 1991-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156822

## Citation

> US National Institutes of Health, RePORTER application 3156822, COLLAGEN GENE EXPRESSION IN CHONDROCYTES IN INFLAMMATION (2R01AR034390-04A1). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3156822. Licensed CC0.

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