# EXTRACELLULAR PROCESSING OF CARTILAGE PROTEOGLYCANS

> **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 1991 · $77,537

## 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 closely
related 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 alkali induced
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:** 3158644
- **Project number:** 5R01AR038580-06
- **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:** 1991
- **Award amount:** $77,537
- **Award type:** 5
- **Project period:** 1989-01-01 → 1993-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158644

## Citation

> US National Institutes of Health, RePORTER application 3158644, EXTRACELLULAR PROCESSING OF CARTILAGE PROTEOGLYCANS (5R01AR038580-06). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3158644. Licensed CC0.

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