# REGULATION OF OSTEOBLAST ACTIVITY

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 1993 · $223,798

## Abstract

The work proposed in this grant application will extend our knowledge
regarding the regulatory aspects of the bone forming cell, the osteoblast.
The main thrust of this work is the description of a new role for type
tartrate resistant acid phosphatase (TRAP).  This enzyme is present in
osteoclasts and at sites of resorption and it is our hypothesis that the
molecule has growth factor-like effects on bone cells.  In preliminary
findings we have shown that a molecule which is homologous to osteoclastic
TRAP can stimulate isolated progenitor osteoblasts to acquire a more
differentiated phenotype.  The significance of such an effect is that TRAP,
due to its location on the resorbing surface, can act as a site-specific
molecule to direct the formation of bone to resorption lacunae.  Thus,
along with other soluble regulatory factors released during osteoclastic
activity TRAP may participate in local bone remodelling.

In the first part of this project we intend 1) to characterize the effects
of TRAP on bone cells and other cells, 2) to investigate whether known
growth factors interact with it, and 3) to determine if it affects the
production of TGF beta and bFGF.  The second part of the project involves
isolating and identifying the TRAP receptor and using the receptor to
further characterize regulatory molecules in bone.  (We currently believe
that the receptor through which TRAP mediates its effects is the IGF-
II/mannose-6-phosphate receptor, but this needs to be proven.)  The last
part of the project explores second messenger signalling mechanisms for
TRAP and the possible role of intracellular calcium as a transducing agent.

The importance of this work is that it may, for the first time, shed light
on the localized nature of the bone remodelling process.  Our central
hypothesis is that the large amount of osteoclastic TRAP which remains on
the surface of resorption lacunae can act as a site-directing regulatory
molecule for the formation of new bone.  These findings may also explain
the high rates of osteoblastic activity in pathological states with high
acid phosphatase content, such as prostate metastases to the skeleton.

## Key facts

- **NIH application ID:** 3155653
- **Project number:** 5R01AR028420-08
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **SAM.gov UEI:** F27KDXZMF9Y8
- **Principal Investigator:** J. Edward PUZAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $223,798
- **Award type:** 5
- **Project period:** 1982-02-01 → 1995-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155653

## Citation

> US National Institutes of Health, RePORTER application 3155653, REGULATION OF OSTEOBLAST ACTIVITY (5R01AR028420-08). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155653. Licensed CC0.

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