# HYALURONIC ACID TYPE-SWITCHING IN CHONDROGENESIS

> **NIH NIH R01** · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · 1989 · $84,917

## Abstract

Previous investigations have shown that synthesis of high
molecular weight hyaluronic acid is not coordinately linked to
synthesis of cartilage-type proteoglycan monomer in cultures of
newly-differentiating chondrocytes.  This data has raised the
hypothesis that synthesis of high molecular weight HA is rate-
limiting for cartilage extracellular matrix synthesis.  As a
corollary, it follows that the matrix requires this particular HA to
become "functional" and that its appearance reflects maturation
of the matrix.  Biosynthetic events leading to high molecular
weight HA could involve switches in HA-type (ie. as collagen-type
switches from type I to type II), alterations in HA-degrading
(hyaluronidase) activity, or changes in de novo synthetic patterns.
The resolution of these alternative mechanisms is a crucial step in
a complete understanding of cartilage matrix development.  The
proposed experiments will investigate these alternative
mechanism by:  1) isolating and characterizing HA synthesis
during de novo chondrogenesis, 2) determining the ability of each
type of isolated HA to bind proteoglycan monomer, and the
kinetics of this association, 3) determining the pattern of
appearance, isoform type, and HA-type specificity of
hyaluronidase, and 4) analyzing the ability of pre-chondrocytes
and chondrocytes to synthesize HA in a cell-free system.  Newly
synthesized HA will be isolated from pre- and postchondrogenic
cultures of skeletal muscle on demineralized bone and
characterized by density, hydrodynamic size, conformation in
solution, and ability to promote aggregation with purified
proteoglycan monomer.  Hyaluronidase activity of these cultures
will be determined against a well-characterized, commercial
preparation of HA followed by an investigation of the activity
against HA-types identified previously.  Cell-free synthesis will
determine the ability of de novo chondrocytes to synthesize HA-
types in the absence of HA-degrading activity.  Control tissues
will include nonchondrogenic (skeletal muscle grown on collagen
gels) and chondrogenic (Swarm rat chondrosarcoma) sources; these
tissues will permit a comparative investigation of HA synthetic
potential.  Data derived from these experiments will provide a
detailed description of HA synthesis during chondrogenesis and of
the mechanism(s) whereby chondrocytes synthesize HA capable of
aggregating with proteoglycan monomers.

## Key facts

- **NIH application ID:** 3158335
- **Project number:** 5R01AR037940-02
- **Recipient organization:** UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
- **Principal Investigator:** MARK A NATHANSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $84,917
- **Award type:** 5
- **Project period:** 1988-07-01 → 1991-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158335

## Citation

> US National Institutes of Health, RePORTER application 3158335, HYALURONIC ACID TYPE-SWITCHING IN CHONDROGENESIS (5R01AR037940-02). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3158335. Licensed CC0.

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