# HORMONAL REGULATION OF OSTEOBLAST FUNCTION

> **NIH NIH R01** · JEWISH HOSPITAL OF SAINT LOUIS · 1990 · $179,293

## Abstract

The long term objective of this project is to analyze the
mechanism by which parathyroid hormone (PTH) controls bone
remodeling and stimulates bone resorption.  The discovery that
PTH does not directly stimulate the osteoclast, but rather
increases resorptive activity through actions in other cells (most
likely osteoblasts) producing factors acting in the local bone
environment to increase osteoclastic activity, has left the
mechanisms of PTH action unresolved.  Since PTH is one of the
most important systemic regulators of bone resorption, knowledge
of its mechanism of action is critical to understanding disease
states of altered bone resorption such as osteoporosis.  Recent
literature, including work of the principal investigator, suggest
that PTH has a bifunctional mechanism of signal transduction.
The PTH-receptor complex couples to adenylate cyclase and
increases 3'5' cAMP production, but it also activates the calcium
messenger system independent of adenylate cyclase activity.  The
specific aims of this project are to characterize stimulation of
the calcium messenger by PTH in osteoblasts.  The calcium
transport mechanisms by which PTH regulates osteoblast cell
calcium will be elucidated.  These studies will involve isotopic
flux studies, microspectrofluorometric determination of cytosolic
Ca2+, microinjection studies and patch clamp recordings of single
ion channels in osteoblasts.  The mechanism of PTH-receptor
coupling to stimulation of the calcium messenger system will be
analyzed.  These studies will involve analysis of PTH receptor
binding, stimulation of phospholipase-C and isolation of the PTH
receptor coupling to phospholipase-C.  Studies in this project will
also analyze the stimulation of osteoblast function by PTH, and
the role of the calcium messenger system in the stimulation.  As a
result this project will carefully analyze the control of osteoblast
function by PTH, and contribute significantly to our understanding
of disease states characterized by increased rates of bone
resorption.

## Key facts

- **NIH application ID:** 3159684
- **Project number:** 5R01AR039561-03
- **Recipient organization:** JEWISH HOSPITAL OF SAINT LOUIS
- **Principal Investigator:** KEITH A HRUSKA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $179,293
- **Award type:** 5
- **Project period:** 1988-07-01 → 1992-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159684

## Citation

> US National Institutes of Health, RePORTER application 3159684, HORMONAL REGULATION OF OSTEOBLAST FUNCTION (5R01AR039561-03). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3159684. Licensed CC0.

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