# MECHANISMS OF ORTHOPEDIC IMPLANT LOOSENING

> **NIH NIH R01** · JEWISH HOSPITAL OF SAINT LOUIS · 1990 · $162,733

## Abstract

Implant loosening remains a major cause of delayed failure in
joint replacement.  Because such loosening occurs as a
consequence of excess bone resorption resolution of this problem
pivots on identifying the cells and resorptive mechanisms involved
in bone matrix degradation.  Recent work from this, and other
laboratories, has shown that (i) osteoclasts resorb bone collagen
using a lysosomal acid protease, (ii) osteoblasts may be involved in
the resorptive phase of remodeling sine, in response to hormones,
they produce both neutral collagenase and a potent collagenase
inhibitor, and (iii) macrophages, which accumulate at sites of
cemented implants, secrete a number of factors, including
Interleukin-1, and prostaglandin E2, capable of stimulating
resorptive activity.  In the present application, experiments are
described aimed at expanding and integrating these observations.
Specifically, we propose to :  (1) ISOLATE AND CHARACTERIZE
THE ENZYME RESPONSIBLE FOR OSTEOCLAST-MEDIATED
COLLAGENOLYSIS, (2) ASSESS THE INTRACELLULAR
PROCESSING AND TRAFFICKING OF THE OSTEOCLAST
COLLAGENOLYTIC ENZYME IN RESORPTIVE AND NON-
RESORPTIVE OSTEOCLASTS, AND (3) EVALUATE THE
CAPACITY OF MACROPHAGES TO (A) MODULATE
OSTEOCLAST RESORPTIVE ACTIVITY AND (B) INFLUENCE
SYNTHESIS OF OSTEOBLAST NEUTRAL COLLAGENASE AND
COLLAGENASE INHIBITOR.

## Key facts

- **NIH application ID:** 3156403
- **Project number:** 5R01AR032788-07
- **Recipient organization:** JEWISH HOSPITAL OF SAINT LOUIS
- **Principal Investigator:** Steven L Teitelbaum
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $162,733
- **Award type:** 5
- **Project period:** 1983-09-01 → 1991-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156403

## Citation

> US National Institutes of Health, RePORTER application 3156403, MECHANISMS OF ORTHOPEDIC IMPLANT LOOSENING (5R01AR032788-07). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3156403. Licensed CC0.

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