# INORGANIC PYROPHOSPHATE METABOLISM IN ARTHRITIS

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 1988 · $98,388

## Abstract

The long-term objective of these studies is to better elucidate the
pathogenesis of calcium pyrophosphate dihydrate (CPPD) crystal
deposition disease, a common form of arthritis, so that logical
approaches to treatment and/or prophylaxis may be formulated.
Disordered inorganic pyrophosphate (PPi) metabolism has been
strongly implicated as a factor in contributing to CPPD crystal
formation in vivo.  Recent reports support this hypothesis by
demonstrating elevated intracellular PPi in cultured cells of a
single kindred with familial CPPD deposition; and elevated
nucleoside triphosphate pyrophosphohydrolase (NTPPPH) activity,
which generates PPi, in CPPD-containing cartilage.  Subsequent
and preliminary studies suggest that:  elevated intracellular PPi is
present in skin-derived fibroblasts from patients with both
sporadic and familial CPPD deposition disease; NTPPPH activity
is elevated in joint fluids and on the surface of cultured cells for
patients with CPPD deposition; NTPPPH on chondrocytes in an
ectoenzyme capable of generating PPi at the extracellular site
where CPPD crystals form in cartilage.

This proposal will specifically aim at determining:  (1) if elevated
intracellular PPi is a valid disease "marker"; (2) the metabolic
source of intracellular PPi; (3) whether elevated ecto-NTPPPH is
also a disease "marker"; (4) whether extracellular substrate is
available in cartilage to interact with ecto-NTPPPH, thereby
generating extracellular PPi; (5) which factors modulate NTPPPH
activity; (6) what physical and biochemical factors affect ppi
elaboration by cartilage.  The knowledge of chondrocyte
ectoenzymes which we glean will be used to devise an in vivo
cartilage organ culture model of CPPD deposition which would
facilitate studies of therapeutic interventions and of the
biochemical effects of crystals in cartilage.

## Key facts

- **NIH application ID:** 3158696
- **Project number:** 5R01AR038656-02
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **SAM.gov UEI:** E8VWJXMMUQ67
- **Principal Investigator:** LAWRENCE M. RYAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $98,388
- **Award type:** 5
- **Project period:** 1987-05-01 → 1992-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158696

## Citation

> US National Institutes of Health, RePORTER application 3158696, INORGANIC PYROPHOSPHATE METABOLISM IN ARTHRITIS (5R01AR038656-02). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3158696. Licensed CC0.

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