# CARTILAGE AUTOCATABOLISM IN INFECTIOUS ARTHRITIS

> **NIH NIH R01** · STANFORD UNIVERSITY · 1989 · $178,562

## Abstract

The purpose of this grant is to characterize the biochemical basis for
articular cartilage autocatabolism.  Specifically, we intend to determine
what enzymatic activities are responsible for the onset of cartilage
destruction.

We have shown that bacteria stimulate proteoglycan loss from cartilage if
living cartilage cells are present.  The initiation of proteoglycan loss is
clearly the first step in cartilage destruction.  We have established this
in animal models of infectious and inflammatory arthritis.  Other
laboratories have shown that cartilage proteoglycan loss can be triggered
by the presence of a low molecular weight protein, catabolin, and that
living cartilage is required.  The question which remains is what
biochemical mechanism supports the proteoglycan degradation.  Is it
proteolytic?  Is it extremely labile or is it present only after some
inductive signal for protein synthesis?  Are a number of enzymatic
activities involved?

To answer these questions we are proposing to trigger cartilage degradation
by bacteria, Staphylococcus aureus, and after specific times, 12, 24 and 48
hours, to homogenize the cartilage and assay for enzymatic activities.  The
enzymes to be studied are glucuronidase, hexosaminidase, alkaline
phosphatase, cathespin D, neutral proteinases and hyaluronidase.  Metabolic
inhibitors will be used to study turnover rates and synthesis patterns of
enzymatic cartilage degrading enzymes.

The significance of this investigation will be to characterize the extent
to which cartilage cells alone contribute to arthritis in response to
extracellular signals.  A cartilage specific response to any foreign
stimulus, in conjunction with immune system reactions, may then be additive
in cartilage destruction in all forms of arthritis.  To effectively control
the arthritic reaction, the biochemical characteristics of chondrocyte
behavior must first be determined.

## Key facts

- **NIH application ID:** 3155896
- **Project number:** 5R01AR030796-06
- **Recipient organization:** STANFORD UNIVERSITY
- **SAM.gov UEI:** HJD6G4D6TJY5
- **Principal Investigator:** R L SMITH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $178,562
- **Award type:** 5
- **Project period:** 1984-06-01 → 1991-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155896

## Citation

> US National Institutes of Health, RePORTER application 3155896, CARTILAGE AUTOCATABOLISM IN INFECTIOUS ARTHRITIS (5R01AR030796-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3155896. Licensed CC0.

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