# OSTEOCALCIN SYNTHESIS AND CATABOLISM IN VIVO AND IN VITR

> **NIH NIH R01** · YALE UNIVERSITY · 1987 · $143,182

## Abstract

Osteocalcin is a small protein comprising 20% of the noncollagenous protein
in the extracellular matrix of bone.  Current studies indicate that it is
derived from higher molecular weight precursors and that its synthesis and
processing is regulated by 1,25(OH)2D3.  It may play a role in regulating
hydroxylapatite crystal growth and recruiting osteoclasts to sites of bone
resorption.  Although investigations into the structure and properties of
osteocalcin have progressed in the past several years, many questions
remain regarding its biosynthesis and catabolism.  In an effort to answer
these questions we intend to:

1) Identify specific precursors of osteocalcin and study the effect of
calcitropic hormones on synthesis and processing using rat and human bone
cells in culture.

2) Identify specific fragments of osteocalcin that are produced during bone
resorption using an organ culture system of devitalized bone and human
peripheral monocytes.

While osteocalcin is found predominantly in bone, traces occur in serum and
levels determined by radioimmunoassay correlate with the rate of bone
formation.  In order to develop serum osteocalcin as a diagnostic marker
for metabolic bone disease, we will:

1) Establish normal values based on age, sex, hormonal status, diet, and
activity.

2) Study the relationship between serum osteocalcin and other indices of
bone metabolism including mineral levels, alkaline phosphatase, urinary
hydroxyproline, calcitropic hormones, and direct histomorphometric
measurements.  These parameters will be assessed in normal individuals and
those with bone disorders.

During osteoclastic bone resorption, fragments of osteocalcin may be
secreted into the circulation.  We will produce monoclonal antibodies to
synthetic and naturally occurring fragments of osteocalcin and test them in
the clinical studies outlined above.

Through these studies, we hope to improve the understanding of the
biosynthesis and catabolism of osteocalcin and its role in calcium
homeostasis and bone metabolism.  We also hope to establish the
measurements of osteocalcin and its fragments as important discriminatory
parameters for the diagnosis of bone disorders.

## Key facts

- **NIH application ID:** 3158562
- **Project number:** 5R01AR038460-02
- **Recipient organization:** YALE UNIVERSITY
- **SAM.gov UEI:** FL6GV84CKN57
- **Principal Investigator:** Caren Gundberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $143,182
- **Award type:** 5
- **Project period:** 1986-07-01 → 1988-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158562

## Citation

> US National Institutes of Health, RePORTER application 3158562, OSTEOCALCIN SYNTHESIS AND CATABOLISM IN VIVO AND IN VITR (5R01AR038460-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158562. Licensed CC0.

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