# DNA SYNTHESIS AND OSTEOCLAST FUNCTION IN BONE

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 1987 · $111,525

## Abstract

This grant proposes to study the relationships between DNA synthesis in
bone cells, alterations in the morphology of osteoclasts and bone
resorption.  The osteoclast is the principal cell which mediates bone
resorption.  Osteoclasts increase their size and number in bone by
incorporating a terminally differentiated cell, the osteoclast precursor.
Production of osteoclast precursor cells is believed to be dependent on the
replication and differentiation of a stem cell.

The projects in this grant will attempt to answer the questions:  1) Do
factors which alter bone resorption affect the replication of the
osteoclast precursor stem cells?  2) Do factors which regulate the
replication of osteoclast precursor stem cells alter bone resorption?  and
3):  What is the relationship between inhibiting cell replication in bone
cells and the production of prostaglandins by these cells.

I will study fetal rat long bone cultures for the effects that known
regulators of bone resorption have on DNA synthesis, osteoclast morphology
and the incorporation of recently replicated nuclei into osteoclasts.
Bones will be cultured with inhibitors of DNA synthesis to determine if
alterations of cell replication influence the resorptive response.  I will
also determine the effects that inhibitors of DNA synthesis have on the
differentiation of cells in organ and cell cultures and on the
concentration of prostaglandins in the medium since I have preliminary
evidence linking increases in medium prostaglandin concentrations with the
inhibition of cell replication.  I will examine conditioned media which
contain granulocyte-monocyte colony stimulating factors to determine if
they alter bone resorption rates or osteoclast morphology.  I will
determine the similarities between the responses of fetal rat long bone
cultures to known stimulators of resorption and the responses to
conditioned media from tumor cell cultures which, in vivo, produce humoral
hypercalcemia.  Finally, I will attempt to develop a cell culture system
which allows rat bone marrow cells to replicate and differentiate into
osteoclast-like cells.

## Key facts

- **NIH application ID:** 3156016
- **Project number:** 5R01AR031263-06
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **SAM.gov UEI:** H6D6JMXJXDE6
- **Principal Investigator:** Joseph A Lorenzo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $111,525
- **Award type:** 5
- **Project period:** 1982-09-30 → 1988-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156016

## Citation

> US National Institutes of Health, RePORTER application 3156016, DNA SYNTHESIS AND OSTEOCLAST FUNCTION IN BONE (5R01AR031263-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156016. Licensed CC0.

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