# MODELING CALCIUM PYROPHOSPHATE CRYSTAL DEPOSITION

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 1988 · $84,003

## Abstract

Calcium pyrophosphate dihydrate (CPPD) deposition disease is
characterized by CPPD crystal deposits in articular and
fibrocartilage, especially knee minisci.  The pathogenesis of
cartilage degeneration in this arthritic disease is thought to
include an amplification loop; damaged cartilage is predisposed
to CPPD crystal deposition which in turn enzymatically or
mechanically further damages the cartilage.  This research
proposal details studies which will use in vitro crystal growth
model systems to assess the effect of collagen and the effect
of whole meniscus fibrocartilage on the formation and growth of
CPPD crystals.

We propose to purify type I collagen from rat tail tendons, to
prepare gels of native-type collagen fibrils, and to use them
in collagen controlled ca and pyrophosphate (PPi) ionic
diffusion model systems for CPPD deposition.  Ionic diffusion
leading to crystal formation will be carried out in two ways:
1) Native collagen gels will be set so that high initial [Ca]
(25 mM) at one end of the gel and high initial [PPi] (10 mM) at
the other must undergo ionic diffusion before crystallizing at
or near physiologic ionic concentrations.  2) CPPD
crystallization in native collagen gels will also be studied
using constant physiologic [Ca] and [PPi] ionic gradients.

We propose to determine if CPPD crystallization is affected by
collagen type.  In addition to type I collagen isolated from
rat tail tendons, we will also purify type II collagen from the
sternal cartilage from lathyritic chicks.  Using our model
system, CPPD crystal growth in these types of collagen will be
compared.  Further, we propose to determine if CPPD crystals
preferentially nucleate on collagen by comparing CPPD
crystallization kinetics in the types I and II collagen gels to
that in gels composed of biological gelatin, silica gel, and
agar.

We propose to monitor the role of the intact versus separated
cartilage components on CPPD crystal formation and growth by
allowing physiological [Ca] and [PPi] solutions to diffuse
through and crystallize in intact menisci cores.  We also
propose to measure crystal turnover during CPPD crystal
formation in intact menisci by injection of 45Ca into the
growth medium and quantitation of both uptake and release of
45Ca as a function of time.

## Key facts

- **NIH application ID:** 3156726
- **Project number:** 5R01AR034096-03
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **SAM.gov UEI:** E8VWJXMMUQ67
- **Principal Investigator:** GRETCHEN S MANDEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $84,003
- **Award type:** 5
- **Project period:** 1986-07-01 → 1990-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156726

## Citation

> US National Institutes of Health, RePORTER application 3156726, MODELING CALCIUM PYROPHOSPHATE CRYSTAL DEPOSITION (5R01AR034096-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156726. Licensed CC0.

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