# COLLAGEN IN OSTEOARTHRITIC CARTILAGE

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 1991 · $177,147

## Abstract

It has been shown that the phenotypic expression of rabbit
articular chondrocytes may be modulated either by continued
subculture or by treatment of primary chondrocytes with retinoic
acid, as monitored by changes in the collagen phenotype.  Although
the two modulated phenotypes differ, both are reversed by treatment
with the microfilament modifying drug dihydrocytochalasin B,
suggesting a common mechanism for the reexpression of the
chondrocyte phenotype, we will investigate the possibility that
modifications in microfilament structure are physically transmit:ed
into the nucleus, by way of cytoskeletal-nuclear matrix
interactions, and result in changes in gene expression, and the
possibility that modification may generate chemical signals
mediated by altered membrane association and phosphorylation by
protein kinase C or tyrosine kinases.

Multiple processes and molecular associations will be tested for
involvement in the microfilament mechanism.  Alterations in the
compartmentalization of cellular proteins will be investigated
using high resolution 2-D protein mapping techniques.  Monoclonal
antibodies to cytoskeletal proteins will be used in their
identification and quantitation.  The cellular distribution and
architectural patterns of cytoskeletal/nuclear-matrix component
will also be investigated using indirect immunofluorescence and
transmission electron microscopy.  Crosslinking analysis will be
used to identify both actin- and DNA-associated proteins, both to
establish the presence or absence of actin within the nucleus and
to study changes in proteins that are likely to be involved in the
mechanism of reexpression.  Additional studies will test the role
of poly-ADP ribosylation, DNA supercoiling, and the requirement for
a serum-derived factor in the reexpression mechanism.

The proposed studies are part of a long term strategy to understand
and manipulate the pathogenesis of osteoarthritis.  Developing an
understanding of the mechanisms of phenotypic change, using this
unique model system, will greatly enhance the probability of future
clinical intervention at natural control points.

## Key facts

- **NIH application ID:** 3154903
- **Project number:** 5R01AR016404-17
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **SAM.gov UEI:** G88KLJR3KYT5
- **Principal Investigator:** Paul David Benya
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $177,147
- **Award type:** 5
- **Project period:** 1977-03-15 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3154903

## Citation

> US National Institutes of Health, RePORTER application 3154903, COLLAGEN IN OSTEOARTHRITIC CARTILAGE (5R01AR016404-17). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3154903. Licensed CC0.

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