# INVESTIGATE THE REGULATION OF BONE RESORPTION

> **NIH NIH R01** · UNIVERSITY OF LONDON · 1990 · $88,642

## Abstract

We plan to isolate  and characterize the factor(s) through which
osteoclasts stimulate osteoclastic resorption by analysis of supernatants
using the isolated osteoclast resorption assay. We will identify the
responsiveness of osteoclasts to cytokines and growth factors, and other
known and potential regulators of bone resorption. The role of second
messengers in the regulation of bone resorption by osteoclasts will be
assessed, and we will identify those matrix components in bone that
mediate adhesion and modulate bone resorption by osteoclasts. The lineage
and regulation of differentiation of the osteoclast will be analyzed
using the primary function of osteoclasts, the excavation of bone,
supported by the osteoclast-specific monoclonal antibodies we have
developed, as criteria for osteoclast-differentiation. Osteoclast lineage
will be identified in semi-solid cultures of bone marrow cells. The
effects of calcium-regulating hormones, cytokines and osteoblastic cells
on osteoclastic development in colonies will be assessed. We will attempt
to identify circulating precursors of osteoclasts in normal individuals
and in patients and laboratory animals with increased levels of
osteolysis by immunocytochemistry and the ability to excavate bone
slices. We will identify leukemias that consist entirely or partially of
osteoclastic precursors, using both fresh peripheral blood cells, and
cells incubated under circumstances that induce osteoclastic
differentiation. We will develop osteoclastic cell lines, since these
could make a major contribution to analysis of the regulation of
osteoclastic function. We propose to exploit our access to
osteoclastomas. These tumours provide an opportunity to identify the
osteoblastic phenotype associated with osteoclastic stimulation. We will
raise monoclonal antibodies to the osteoblastic cells in these tumors,
and develop cell lines which will further enable characterization of this
phenotype. We propose to use osteoclasts from these tumors, as the only
practicable source of human osteoclasts, to test the responsiveness of
human osteoclasts, particularly to cytokines and growth factors that show
species specificity. The tumors also represent a bulk of osteoclasts
otherwise unavailable in mammals, from which we propose to purify and
characterize the enzymes that resorb bone, with a view to identification
of characteristics that may be amenable to therapeutic intervention, and
to the development of novel markers for the measurement of resorptive
activity in vitro and in vivo.

## Key facts

- **NIH application ID:** 3159806
- **Project number:** 5R01AR039623-02
- **Recipient organization:** UNIVERSITY OF LONDON
- **Principal Investigator:** TIMOTHY J CHAMBERS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $88,642
- **Award type:** 5
- **Project period:** 1989-09-30 → 1992-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159806

## Citation

> US National Institutes of Health, RePORTER application 3159806, INVESTIGATE THE REGULATION OF BONE RESORPTION (5R01AR039623-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3159806. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*