# METABOLISM OF NONCOLLAGENOUS BONE PROTEINS

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 1990 · $106,843

## Abstract

Two related questions are investigated in this proposal.  First,
what is the biological function of the vitamin K-dependent, bone
specific protein, bone Gla protein (BGP, Osteocalcin)?  BGP is an
abundant, noncollagenous protein which comprises approximately
1-2% of the total proteins present.  A number of key experiments
point to the function and control of biosynthesis of BGP.  BGP is
found in minute quantities in the circulation, and the levels are
altered in metabolic bone diseases.  Bone Gla protein requires its
full complement of 3 delta-carboxyglutamic acid residues in order
to bind to the bone mineral phase, as treatment with the vitamin
K antagonist warfarin abolishes the delta-carboxylation of BGP
and its mineral binding capacity.  Thus, rats treated with warfarin
do not accumulate BGP in bone, although they continue to grow
normally.  The post translational delta-carboxylation of BGP is
essential for its normal intracellular processing and secretion
from the cell.  Bone culture experiments have shown that this
protein is made in bone by osteoblasts, and is synthesized at a
rate comparable to type I collagen.  When vitamin D metabolites
are added to cultures, collagen synthesis and bone Gla protein
synthesis are regulated in opposite directions.  Bone Gla protein
levels in bone and serum decline with age, as does the capacity to
form new bone.  The second, related question is, why does bone
formation rate and osteoblastic function decline in aged rats.
Either the bone formation rate or the bone resorption rat or both
are abnormal in osteoporosis.  We propose to determine if stem
cell depletion or a loss of systemic factors are the cause of the
decreased bone formation in the old rat.

A specific radioimmunoassay for BGP will be combined with in
vivo and in vitro experiments to explore the biosynthesis and
function of this protein.  Two model systems, one in vivo, and one
in vitro will be used to test for stem cell activity from rats of
different ages.

## Key facts

- **NIH application ID:** 3157021
- **Project number:** 5R01AR035056-06
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **SAM.gov UEI:** X1M1PN3KG3E7
- **Principal Investigator:** SATORU Kenneth NISHIMOTO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $106,843
- **Award type:** 5
- **Project period:** 1988-07-15 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3157021

## Citation

> US National Institutes of Health, RePORTER application 3157021, METABOLISM OF NONCOLLAGENOUS BONE PROTEINS (5R01AR035056-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3157021. Licensed CC0.

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