# PARATHYROID HORMONE REGULATION OF OSTEOBLASTIC MRNA

> **NIH NIH R01** · SAINT LOUIS UNIVERSITY · 1989 · $95,801

## Abstract

Skeletal remodelling may be defined as the balanced interaction
of the processes of bone formation and resorption in the adult
animal.  Disruption of this balance results in a number of
skeletal disorders such as, osteoporosis, osteopetrosis and
osteosclerosis.  The essential mechanisms underlying the
remodelling process have to do with the regulation of bone matrix
synthesis and degradation.  It has been known for many years that
the cell in bone responsible for synthesizing matrix is the
osteoblast.  Recently, a body of information has accrued
indicating that the osteoblast plays a pivotal role in bone
resorption as well as formation.  This has included its
identification as the target and mediatory cell for many bone-
resorbing agents, in particular, parathyroid hormone (PTH).  One
consequence of PTH action is a reduction in the synthesis of type
I collagen, the major organic component of bone matrix.  In
previous and preliminary studies, we have confirmed this
observation using the osteoblastic tumor cell line, UMR 106-01.
Specifically, we have found that exposure of UMR cells to PTH
results in a 40% decline in the rate of collagen synthesis and a
95% reduction in procollagen mRNA abundance.  Moreover, in
nuclear runoff and procollagen chimeric gene transient
transfection experiments, we have established that the latter
reduction in message level is not due to PTH-induced alterations
in transcriptional activity leading us to formulate the
hypothesis that PTH regulates gene expression in UMR cells by
controlling messenger stability.  The aims of the present
proposal are to test and clarify this hypothesis by, 1) directly
measuring procollagen mRNA half-life in control and PTH-treated
cells.  2) assessing whether such messenger degradation occurs in
ribonucleoprotein (RNP) particles, free polysomes or polysomes
associated with the endoplasmic reticulum and whether there is
localization of procollagen transcripts to any of these
compartments, 3) investigating whether protein synthesis is an
obligate part of the mRNA degradation process and, if so, 4)
determining whether a specific "RNase" is responsible for
procollagen transcript turnover, and, finally, 5) testing whether
it is cAMP, diacylglcerol or Ca2+ that is the effective second
messenger of PTH in regulating procollagen mRNA abundance and
stability.  Our overall goal, the determination of the site and
mechanism of turnover of collagen transcripts, should shed light
on the action of PTH on the osteoblast.

## Key facts

- **NIH application ID:** 3159971
- **Project number:** 1R01AR039743-01
- **Recipient organization:** SAINT LOUIS UNIVERSITY
- **SAM.gov UEI:** JNBLLTBTLLD8
- **Principal Investigator:** Nicola C Partridge
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $95,801
- **Award type:** 1
- **Project period:** 1989-01-01 → 1993-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159971

## Citation

> US National Institutes of Health, RePORTER application 3159971, PARATHYROID HORMONE REGULATION OF OSTEOBLASTIC MRNA (1R01AR039743-01). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3159971. Licensed CC0.

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