# CELLULAR MECHANISMS OF BONE RESORPTION

> **NIH NIH R01** · JEWISH HOSPITAL OF SAINT LOUIS · 1992 · $200,593

## Abstract

Osteoporosis always reflects enhanced osteoclastic relative to
osteoblastic activity and hence, the long term goals of this project
have been elucidation of the cellular mechanisms of bone resorption.
Significant progress has been made in the last five years reflecting,
in particular, the development of models whereby highly enriched
populations of osteoclasts can be studied in vitro.  Using such
models, we have shown that bone resorption is a multistep process
initiated by osteoclast-matrix recognition and attachment.  In fact,
it is now clear that the capacity of the cell to degrade bone
ultimately depends upon its matrix binding ability.

Recent evidence implicates integrins as the major class of molecules
mediating cell-matrix recognition and attachment and we and others
have shown that such is the case as regards the osteoclast.  In
particular, the integrin alphav/beta3 whose expression, we find, is
regulated by the osteoclastogenic hormone, 1,25-dihydroxyvitamin D3,
appears to be the major modulator of osteoclast-bone binding and bone
resorption.  It is also now evident that integrins, in addition to
their attachment functions, are capable of initiating intracellular
signalling when interacting with specific matrix proteins or
peptides.  As evidenced by our preliminary data, such is true as
regards the osteoclast.  Thus, our efforts will be aimed at studying
the biology of integrins in the osteoclast as well as determining
mechanisms whereby their function in vivo modulates osteoclast
recruitment and bone resorption.  We therefore specifically propose
to:  1) investigate the mechanisms by which 1,25-dihydroxyvitamin d3
regulates integrin expression during osteoclastogenesis, 2) explore
the relationship between bone matrix recognition by osteoclasts and
delivery of a collagenolytic enzyme to the resorptive
microenvironment; and 3) determine if regulation of integrin function
modulates osteoclast recruitment and resorptive activity in vivo.

## Key facts

- **NIH application ID:** 3156400
- **Project number:** 2R01AR032788-09
- **Recipient organization:** JEWISH HOSPITAL OF SAINT LOUIS
- **Principal Investigator:** Steven L Teitelbaum
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $200,593
- **Award type:** 2
- **Project period:** 1983-09-01 → 1996-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156400

## Citation

> US National Institutes of Health, RePORTER application 3156400, CELLULAR MECHANISMS OF BONE RESORPTION (2R01AR032788-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156400. Licensed CC0.

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