# SYNTHESIS OF OSTEOCALCIN IN BONE

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 1989 · $195,416

## Abstract

This renewal application focuses on studies to define the
regulation of synthesis of the vitamin K dependent bone protein,
osteocalcin by three factors which we believe are key to
understanding its function.  1) the role of the pro-piece of
osteocalcin in regulation of osteocalcin secretion, cleavage and
Gla synthesis;  2) the precise function of Gla residue synthesis in
osteocalcin and the requirements for vitamin K utilization in bone
cells for Gla synthesis; and 3) specific definition of the induction
of osteocalcin synthesis by calcitriol as related solely to cellular
level of transcripts and/or to accelerated processing via the
carboxylase enzyme and functionally to bone resorption.  To
achieve these objectives, specific questions of investigation are
the following:  a) the site (e.g., Golgi, microsomes, extracellular)
of propiece cleavage and the mechanism (e.g., serine protease) of
cleavage will be investigated;  b) prove that the propiece is
glycosylated and is a signal for secretion;  c) define the effect of
warfarin on the bone vitamin K cycle, intracellular precursor
accumulation and osteocalcin peptide synthesis; d) determine the
requirement of and precise number of Gla residues for pro-
osteocalcin cleavage and osteocalcin function.  The majority of
the proposed studies will be carried our in a newly developed
chick osteoblast culture system in which second passage cells
(greater than 90% pure osteoblasts) undergo a programmed
differentiation throughout a 3 week culture period producing a
matrix that calcifies even in the absence of a chemical inductant.
In this system pro-osteocalcin and osteocalcin function can be
addressed by examining alterations in matrix formation, mineral
deposition and bone cell activity (measuring parameters of
alkaline phosphatase and collagen synthesis) that result from 1)
inhibition of propeptide cleavage; 2) inhibition of pro-osteocalcin
secretion;  3) inhibition of Gla synthesis in the protein by
warfarin; and 4) the induction of osteocalcin synthesis by
calcitriol.  Utilizing a cDNA probe of osteocalcin, mRNA levels
and activity will be quantitated as affected by warfarin and
calcitriol and how inhibition of these regulative factors effect
bone cell activity and calcified matrix formation, will allow us to
better define its function and thereby provide a more meaningful
parameter of osteocalcin measurements in a clinical setting.

## Key facts

- **NIH application ID:** 3156682
- **Project number:** 7R01AR033920-06
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **SAM.gov UEI:** MQE2JHHJW9Q8
- **Principal Investigator:** Jane B. Lian
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $195,416
- **Award type:** 7
- **Project period:** 1989-04-01 → 1992-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156682

## Citation

> US National Institutes of Health, RePORTER application 3156682, SYNTHESIS OF OSTEOCALCIN IN BONE (7R01AR033920-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156682. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*