# METABOLISM IN NORMAL AND OSTEOARTHRITIC CARTILAGE

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 1993 · $311,692

## Abstract

The objective of this proposal is to obtain a better understanding of those
processes regulating the degradation and remodeling of cartilage matrix.
We propose to determine how abnormalities in the regulatory metabolic
pathways of osteoarthritic articular cartilage are involved in the etiology
and pathogenesis of the disease.  The experimental design is based on the
hypothesis that interleukin-1 (IL1) and other cytokines are involved in
cartilage remodeling and when produced in excess may lead to the subsequent
joint destruction of osteoarthritis.

Previous work on this grant has resulted in the isolation and
characterization of a cartilage degrading enzyme, presently referred to as
stromelysin or matrix metalloprotease 3 (MMP-3), the major cartilage
degrading protease induced by IL-1.  Studies will be performed to determine
how this enzyme, secreted in a latent inactive form, is activated
endogenously; and we will seek the factors which control its activation.
Protein sequence data already obtained will be used for synthesis of
oligonucleotide probes.  In addition we have recently obtained a cDNA to
the stromelysin mRNA.  The DNA probes will be used in studying the
regulatory mechanisms of stromelysin biosynthesis and to detect and
quantitate its mRNA in normal and diseased cartilage tissue.

We further propose to measure IL-1 in synovial fluid of normal and
osteoarthritic patients; and using.DNA probes, measure messenger RNA coding
for IL-1 in normal and osteoarthritic chondrocytes.  The receptors for this
cytokine on normal and OA chondrocytes will be quantitated.

Further definition of these cartilage metabolic pathways are of primary
importance in our understanding of osteoarthritis.

## Key facts

- **NIH application ID:** 3154893
- **Project number:** 5R01AR016265-19
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **SAM.gov UEI:** FLJ7DQKLL226
- **Principal Investigator:** BENJAMIN V TREADWELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $311,692
- **Award type:** 5
- **Project period:** 1977-04-01 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3154893

## Citation

> US National Institutes of Health, RePORTER application 3154893, METABOLISM IN NORMAL AND OSTEOARTHRITIC CARTILAGE (5R01AR016265-19). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3154893. Licensed CC0.

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