# HORMONAL REGULATION OF BONE CELL FUNCTION

> **NIH NIH R01** · JEWISH HOSPITAL OF SAINT LOUIS · 1993 · $193,409

## Abstract

The long term objective of this project is to analyze the mechanisms 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 its actions
in other cells (most likely osteoblasts), 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.  In addition, the means by which PTH augments bone
formation through actions in the same lineage of cells it uses to encode
messages augmenting resorption is unclear.  Recent work of the principal
investigator, supported through the initial funding cycle of this
application has demonstrated a bi-functional mechanism of signal
transduction activated by PTH.  The PTH-receptor complex couples to
adenylate cyclase increasing cAMP production, but it also activates a
phospholipase-C leading to production of inositol phosphates,
diacylglycerol, and transient elevations of cytosolic calcium.  The
specific aims of the renewal application are to analyze the
phospholipase-C activated by PTH in osteoblasts, and determine the role
of this message system in osteoblast function.  Studies examining
activation of phospholipase C at specific stages in the cell cycle and at
different stages of osteoblast differentiation may provide critical
information regarding the anabolic potential of PTH.  To examine whether
the anabolic effects of PTH on bone formation are transmitted by
augmentation of load induced signals, the interaction between physical
strain induced osteoblast function and PTH will be analyzed.  The studies
in the proposal involve analysis of [Ca2+]i stimulated by PTH using
digital imaging microscopy, patch-clamp recordings of single ion channels
in osteoblast, analysis of the effects of PTH on cell-cell contact and
communication, and characterization of the components of phospholipase-C
activated by PTH.  The latter studies will include the use of molecular
biologic approaches to determine the nature of the phospholipase-C
activated by PTH and characterize the GTP binding proteins associated
with the PTH receptor-phospholipase-C complex.  The studies proposed in
this application, will improve our understanding of osteoblast function
regulated by PTH through phospholipase-C.  The studies will contribute
significantly to our understanding of disease states characterized by
alterations in PTH function, i.e. osteoporosis and renal osteodystrophy.

## Key facts

- **NIH application ID:** 3159686
- **Project number:** 5R01AR039561-06
- **Recipient organization:** JEWISH HOSPITAL OF SAINT LOUIS
- **Principal Investigator:** KEITH A HRUSKA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $193,409
- **Award type:** 5
- **Project period:** 1988-07-01 → 1996-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159686

## Citation

> US National Institutes of Health, RePORTER application 3159686, HORMONAL REGULATION OF BONE CELL FUNCTION (5R01AR039561-06). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3159686. Licensed CC0.

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