# HORMONE REGULATION OF BONE COLLAGEN SYNTHESIS

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 1987 · $194,007

## Abstract

Type I collagen is one of a few proteins that is produced constitutively in
certain cell types and in a highly regulated manner in others.  This grant
is designed to understand the molecular basis by which a different cell
type can express the identical Alpha1(I) and Alpha2(I) collagen genes in a
tissue specific manner.  Using osteoblasts in organ culture, primary
cultured osteoblasts, osteosarcoma cells and fibroblastic cells, the
regulation of type I collagen mRNA will be ascessed using cDNA probes to
Alpha1(I) and Alpha2(I) collagen mRNA and dot hybridization.  Changes in
the cytoplasmic levels of collagen mRNA brought on by PTH, 1,25
dihydroxyvitamin D (1,25(OH)2D3) and insulin will be explained by
alteration in the nuclear transcription of the type I collagen genes and
the half-life of its cytoplasmic mRNA.  In situations where the mRNA change
results from a difference in gene transcription, the structure of the
promoter region of the gene will be examined.  We plan to identify and
characterize the 5' flanking region of the Alpha1(I) and Alpha2(I) collagen
gene.  With these probes subcloned into M13, differences in the domains of
DNAse I sensitivity will be contrasted in each cell type.  Detailed
analysis of the 1,25(OH)2D3 binding site by a filter binding assay and
footprinting technique will use purified 1,25(OH)2D3 receptor complex and
defined DNA segments from the promoter region.  This promoter region will
be placed in a gene transfer vector derived from the bovine papilloma virus
(BPV).  The activity of the collagen promotor will be determined by the
production of a marker protein, human metallothionein, that is a part of
the BPV vector.  The fusion gene will be transferred to the various cell
types to determine if the promoter attains the same regulation and
conformation as the actual promoter.  If the two promoters are similar in
the same cell, then the PBV model will be used to map the domain of the
promoter or enhancer necessary for cell specific activity and hormone
responsiveness.  The model has the potential for isolating factors that are
associated with the cell specific regulation of the promoter and for
reconstituting a regulated in vitro transcription system.

## Key facts

- **NIH application ID:** 3155733
- **Project number:** 5R01AR029983-07
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **SAM.gov UEI:** H6D6JMXJXDE6
- **Principal Investigator:** David W. Rowe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $194,007
- **Award type:** 5
- **Project period:** 1981-08-01 → 1989-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155733

## Citation

> US National Institutes of Health, RePORTER application 3155733, HORMONE REGULATION OF BONE COLLAGEN SYNTHESIS (5R01AR029983-07). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155733. Licensed CC0.

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