# BONE CELL CALCIUM REGULATION

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 1992 · $176,983

## Abstract

The long-term objective of this study Is to understand the factors
regulating osteoblastic cell calcium.  It is becoming increasingly
evident that changes In this ion are involved in the mechanism of action
of several resorptive agents and that an understanding of the various
calcium regulatory systems will aid in the development of potential ways
to control pathological changes in bone metabolism occurring systemically
or locally.  Specifically, it is proposed in osteoblastic cells isolated
from the calvaria of newborn rats and In the osteoblastic human
osteosarcomal cell lines, SaOS-2 and G292, to: 1. to  further study the
nature of the regulation of mobilization of calcium from intracellular
pools with particular emphasis on the role of guanine trisphosphate and
Its possible interaction with inositol phosphates such as 1(1,4,5)p3; 2.
to delineate the nature of regulation of phosphoinositide metabolism and
cytosolic calcium levels by the bone resorptive agent and mitogen,
epidermal growth factor (EGF), in order to better compare and contrast
its effects with other bone resorptive agents such as thrombin; 3. to
delineate the nature of regulation of phosphoinositide metabolism by
calcium via experimentation with calcium channel antagonists, an
ionophore and extracellular calcium levels; 4. to study the
electrophysiological properties of these cells with emphasis on membrane
potential and potassium, sodium and calcium currents; 5. to study the
effects of EGF and thrombin on these electrophysiological properties; 6.
to study the effects of inositol phosphates on the electrophysiological
properties defined in aims 4 & 5; 7. to study the role of tyrosine kinase
activity in the regulation of osteoblastic cell calcium, phosphoinositide
metabolism as well as proliferation In response to EGF.  Cytosolic
calcium regulation will be studied with the fluorescent dye, Fura-2, and
phosphoinositide metabolism in tritiated -inositol labelled cells by
means of high performance liquid chromatography. Cell proliferation will
be assessed by incorporation of tritiated thymidine.  The
electrophysiological properties will be studied with patch-clamp
techniques.  In general, the studies proposed here should provide more In
depth information on the intracellular and plasma membrane regulatory
mechanisms involved in the control of osteoblastic cell calcium with
emphasis. on the possible diversities of these pathways involved upon
activation by agents as potentially different as EGF and thrombin.

## Key facts

- **NIH application ID:** 3155294
- **Project number:** 5R01AR025271-14
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **SAM.gov UEI:** LMCJKRFW5R81
- **Principal Investigator:** ROSEMARY Mary DZIAK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $176,983
- **Award type:** 5
- **Project period:** 1988-04-01 → 1994-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155294

## Citation

> US National Institutes of Health, RePORTER application 3155294, BONE CELL CALCIUM REGULATION (5R01AR025271-14). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155294. Licensed CC0.

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