# ROLE OF PHOSPHOLIPIDS IN MINERALIZATION OF OSTEOID

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 1991 · $203,103

## Abstract

Long bone growth results from a delicately synchronized sequence of events
involving the differentiation of three groups of specialized chondrocytes.
The ultimate chondrocyte is greatly hypertrophied and is believed to direct
the invasion of capillaries and subsequent calcification.  In rats that are
deficient in vitamin D and phosphate, these events are reversibly altered,
capillary invasion is reduced and the growth plate becomes greatly
expanded; this model allows for (1) biochemical analysis of the cell types
that make up the growth plate and (2) induction of capillary invasion and
calcification by treatment with vitamin D and phosphate.

The central premise of these studies is that hypertrophic chondrocytes are
responsible for directing calcification and, in particular, the directed
migration of capillary endothelial cells.  The presence of various growth
factors known to induce or regulate endothelial cell chemotaxis, such as
acidic fibroblast growth factors (aFGF), basic fibroblast growth factor
(bFGF), platelet derived growth factor (PDGF, transforming growth factor-
beta-1 (TGF-beta-1), and endothelial cell stimulating angiogenesis factor
(ESAF), will be determined.  Studies will be performed on tissues, cell or
organ cultures, and co-cultures.  Growth factor localization and
characterization will be based on the results of endothelial cell
chemotaxis assays of extracted tissues and culture media after heparin-
Sepharose chromatography, Western blots of isolated growth factors and
immunolocalization with specific antibodies.  Relative mRNA levels for each
growth factor will be determined by Northern analysis.  Reversal of rickets
(induction of capillary invasion) by vitamin D, its metabolites, and PTH
will be used to study growth factor regulation.

The overall goal of the research program is to elucidate the final common
pathways leading to osteoarthritis (OA) which may be amenable to
therapeutic intervention.  Articular cartilage injury may initiate a
cascade of events that result in increased metalloproteinase production,
followed by a change in joint congruity.  These changes result in small
endochondral growth centers (i.e.:  hypertrophic spurs) beneath the
articular cartilage which appear very similar to growth plate and which
result in a narrowing of the hyaline cartilage.  With increased
understanding of how growth plate calcification occurs, it is hoped that
additional sites for therapeutic intervention in OA will be found.

## Key facts

- **NIH application ID:** 3154676
- **Project number:** 5R01AR008662-26
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **SAM.gov UEI:** F8THLJQSAF93
- **Principal Investigator:** DAVID S HOWELL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $203,103
- **Award type:** 5
- **Project period:** 1974-09-01 → 1995-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3154676

## Citation

> US National Institutes of Health, RePORTER application 3154676, ROLE OF PHOSPHOLIPIDS IN MINERALIZATION OF OSTEOID (5R01AR008662-26). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3154676. Licensed CC0.

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