# INFECTIOUS ARTHRITIS AND CARTILAGE DESTRUCTION

> **NIH NIH R01** · STANFORD UNIVERSITY · 1991 · $197,883

## Abstract

The long-term objectives of this proposal are to define the
biochemical mechanisms underlying continued cartilage degradation in
staphylococcal septic arthritis and to develop therapeutic regimens to
prevent post-infectious inflammatory cartilage destruction.  The
experimental rationale is based on our results showing that
staphylococcal joint infection results in the rapid onset of cartilage
degradation and in persistent cartilage destruction in spite of early
antibiotic treatment.  Addition of an anti-inflammatory agent with
antibiotic therapy decreases but does not override the processes of
cartilage degradation.  The results of these studies are applicable to
rheumatology, orthopaedics and infectious diseases.
     The hypothesis to be tested is that reduction of inflammatory
post-infectious cartilage degradation is analogous to treatment of cancer
in which a combination of therapeutic modalities are required to achieve
successful results.  The multifactorial approach includes synovial lavage
to decrease the levels of debris and inflammatory exudate.  The efficacy
of wash techniques will be expanded by application of systemic and
intra-articular agents to block cartilage degradation and synovial
inflammation.
     The Specific Aims are to: (1) Characterize the
Staphylococcal-induced cartilage degradation following antibiotic and
NSAID therapy in conjunction with lavage at 2, 4 and 7 days after
infection.  Analysis of the cartilage will be carried out (la) at 10 days
post-infection to establish short-term proteoglycan losses and (lb) at
three weeks, seven weeks and three months post-infection to determine
long-term events; (2) Extend the combination treatment by analyzing the
effects of adding two different proteinase inhibitors in the lavage
solution, one an analog of tissue inhibitor of metalloproteinase
(TIMP-like) and the other, alpha 2-macroglobulin; (3) Extend the
combination treatment by adding transforming growth factor beta to
enhance cartilage repair and by adding antibodies to purified
staphylococcal cartilage degrading factor (Staph Factor) in vitro and in
vivo; (4) Expand wash techniques and induce reparative properties to the
cartilage and synovium by adding insulin, epidermal growth factor and
insulin-like growth factor I to (4a) cartilage explant cultures
challenged with Staph Factor and (4b) in the infected joint in a lavage
solution at a stage after bacteria are killed and inflammation has
subsided.
     Experiments will use in vitro and in vivo models of Staphylococcal
infectious arthritis.  Effects of antibiotic and anti-inflammatory
therapies coupled with (a) proteinase inhibitors and (b) growth factors
will be assessed by quantitation of cartilage proteoglycan synthesis and
degradation.

## Key facts

- **NIH application ID:** 3155458
- **Project number:** 2R01AR026833-10
- **Recipient organization:** STANFORD UNIVERSITY
- **SAM.gov UEI:** HJD6G4D6TJY5
- **Principal Investigator:** DAVID J SCHURMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $197,883
- **Award type:** 2
- **Project period:** 1988-07-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155458

## Citation

> US National Institutes of Health, RePORTER application 3155458, INFECTIOUS ARTHRITIS AND CARTILAGE DESTRUCTION (2R01AR026833-10). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155458. Licensed CC0.

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