# CELL SURFACE & OSTEOCLAST DEVELOPMENT

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 1993 · $205,821

## Abstract

Normal bone growth and remodeling are, in part, dependent upon factors
that influence the number and activity of osteoclasts.  Skeletal
pathologies may result from alterations in the osteoclast plasma membrane
or in signals that govern osteoclast cytodifferentiation and resorptive
activity.  Despite substantial recent insights into understanding the
hematopoietic lineage and the interactions of local and systemic
modulators of osteoclast development and function, many questions remain.
In addition, the biochemical and molecular profile of the mature
osteoclast is incomplete.  The hypothesis upon which this application is
based proposes that osteoclast development entails specific cell surface
alterations and that discrete membrane-associated molecules are involved
in osteoclast regulation and function.  The specific aims of this
proposal are to: 1) further characterize the antigen reactive with the
121F monoclonal antibody (MAb) and to clarify its relationship with
superoxide dismutase, 2) continue to identify and biochemically describe
distinct osteoclast plasma membrane molecules recognized by a panel of
osteoclast-specific MAbs, 3) investigate cell surface changes associated
with osteoclast development and functional state, relative to the effects
of known modulators of osteoclast development and activity (such as
estradiol, calcitonin, interleukins 1 and 6, and TNF) and to the induced
expression of protooncogenes (c-fos, c-jun, and c-src), and 4) identify
osteoclast precursors and define stages of osteoclast cytodifferentiation
using-these cell surface markers and molecular probes.  Highly purified
chick osteoclasts and a human leukemic cell line (FLG 29.1) will be used
as sources for chicken and human antigens.  In other experiments, marrow
mononuclear cells which fuse to form multinucleated osteoclast-like giant
cells in culture will serve as a developmental system in which to
investigate the influence of known bone modulators on antigen expression
and resorptive capability, and to define osteoclast precursors.
Biochemical,physiological, immunohistochemical, and molecular cloning
techniques will be employed to ascertain the nature and functional role
of these antigens.  Western and northern blot analyses will be used to
examine their relationship to protooncogene expression.  These results
should not only expand our basic understanding of the cellular and
molecular biology of the osteoclast, but also potentially aid in devising
appropriate preventative and therapeutic strategies for the skeletal
osteopenia of arthritis, osteoporosis, periodontal disease, and other
local or metabolic disorders of bone.

## Key facts

- **NIH application ID:** 3156445
- **Project number:** 5R01AR032927-10
- **Recipient organization:** WASHINGTON UNIVERSITY
- **SAM.gov UEI:** L6NFUM28LQM5
- **Principal Investigator:** Philip A Osdoby
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $205,821
- **Award type:** 5
- **Project period:** 1984-07-01 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156445

## Citation

> US National Institutes of Health, RePORTER application 3156445, CELL SURFACE & OSTEOCLAST DEVELOPMENT (5R01AR032927-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156445. Licensed CC0.

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