# CELL-SUBSTRATE ATTACHMENT IN BONE RESORPTION

> **NIH NIH R01** · JEWISH HOSPITAL OF SAINT LOUIS · 1987 · $85,254

## Abstract

Inappropriate enhancement and diminution in the activity of bone resorbing
cells are important causal factors in the pathophysiology of most metabolic
diseases of bone.  For example, osteopenia and osteopetrosis are,
respectively, associated with increased or decreased levels of bone matrix
degradation.  It follows, therefore, that the establishment of rational
therapies for the treatment of these disorders will depend upon developing
a fuller understanding of the resorption mechanism.

Bone resorption is a complex, multistage process initiated by the
attachment of resorptive cells (or their immediate precursors) to the bone
matrix.  Previous studies of the latter phenomenon have revealed that:  a)
attachment and resorption are properties of relatively well differentiated
cells; b) resorptive efficiency is paralleled by cell-bone binding; c)
carbohydrates (oligosaccharides) on both cells and bone matrix are
essential for attachment; d) glucocorticoids stimulate resorption by
macrophages (and, perhaps, related cell types) by increasing binding
efficiency; e) glucocorticoids increase binding by altering the exposure of
specific membrane sugars.  We now seem to be in particularly favorable
position to extend our understanding of attachment/resorption mechanisms.
The essential experimental techniques are largely in hand, at least one
major component of the attachment mechanism has been identified (cell
membrane sugars), and chemical agents (glucocorticoids) have been assessed
which specifically modify both cell-bone binding and the cell membrane.
Given this base, we propose to:  1) determine if osteoclasts and macrophage
polykaryons attach to bone by the same mechanisms as macrophages; 2)
isolate and identify the "core" protein(s) of bone "attachment"
glycoproteins; 3) characterize the oligosaccharides associated with such
glycoproteins; 4) establish the mechanisms by which glucocorticoids
modulate binding and, in particular, the molecules associated with
attachment; and 5) determine whether changes in membrane lipid composition
and fluidity play a major role in glucocorticoid-stimulated cell-bone
binding.

## Key facts

- **NIH application ID:** 3156838
- **Project number:** 7R01AR034401-03
- **Recipient organization:** JEWISH HOSPITAL OF SAINT LOUIS
- **Principal Investigator:** Steven L Teitelbaum
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $85,254
- **Award type:** 7
- **Project period:** 1987-04-01 → 1988-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156838

## Citation

> US National Institutes of Health, RePORTER application 3156838, CELL-SUBSTRATE ATTACHMENT IN BONE RESORPTION (7R01AR034401-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156838. Licensed CC0.

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