# EXTRACELLULAR PROCESSING OF CARTILAGE PROTEOGLYCANS

> **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 1990 · $73,882

## Abstract

The major clinical features of osteoarthritis are focal loss of
articular cartilage and osteophytic outgrowth of subchondral
bone.  Loss of articular cartilage is preceded by changes in the
content and composition of cartilage matrix proteoglycan
aggregates.  Mature chondrocytes, although biosynthetically
active, appear unable to maintain or repair matrix aggregates so
that cartilage degeneration is progressive.

Proteoglycan aggregates are composed of monomers, link protein
and hyaluronate in ternary complex.  Monomers bind to
hyaluronate (and link protein) via a specific binding region and
this process immobilizes the molecules and possibly protects them
from proteolytic attack.   An understanding of how proteoglycans
acquire hyaluronate binding properties and what occurs during loss
of binding is therefore central to the question of matrix
maintenance in normal and diseased cartilages. Three
closelyrelated systems will be studied (1) rabbit chondrocytes in
monolayer culture which secrete a "precursor" form of
proteoglycan with a low affinity for hyaluronate, which can be
markedly enhanced by treatment in vitro with mild alkali.  We
plan to study conditions of culture which modify precursor
affinity and the molecular basis of the alkaliinduced change in
binding activity.  (2) a cartilage explant system in which the
hyaluronate binding activity of proteoglycans is lost.  This appears
to be due to limited proteoysis of the binding region domain and
we plan to investigate the change in binding region structure. (3)
Purified stromelysin, a neutral metalloendopeptidase, will be
incubated with binding region to determine its effect on the
binding properties and structure of this protein.  Essential
methodologies are established in our laboratory (culture systems,
proteoglycan isolation, immunoassay, binding affinity assays,
electrophoresis and blotting) and we are developing reversed-
phase HPLC for mapping of peptides in proteoglycan core protein.

The long-term objective of these studies is to increase our
understanding of the extracellular processing of cartilage
proteoglycans, particularly in relation to modification of
hyaluronate binding activity.  Such knowledge might suggest
methods for the useful intervention in joint disease at the level of
improving matrix repair by mature chondrocytes.

## Key facts

- **NIH application ID:** 3158643
- **Project number:** 5R01AR038580-05
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **SAM.gov UEI:** NKAZLXLL7Z91
- **Principal Investigator:** JOHN D. SANDY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $73,882
- **Award type:** 5
- **Project period:** 1989-01-01 → 1992-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158643

## Citation

> US National Institutes of Health, RePORTER application 3158643, EXTRACELLULAR PROCESSING OF CARTILAGE PROTEOGLYCANS (5R01AR038580-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158643. Licensed CC0.

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