# OSTEOCALCIN FUNCTION IN RESORPTION

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 1987 · $108,404

## Abstract

Osteocalcin, the major noncollagenous bone protein, characterized by the
vitamin K-dependent calcium-binding amino acid, Gamma-carboxyglutamic acid
(G1a) has well-defined molecular and physical properties.  Recently, it has
been found that bone that is 99% deficient in osteocalcin and 93% deficient
in Gla is poorly resorbed both in vivo, when implanted subcutaneously in a
rat model, and in vitro, when incubated with human monocytes.  These
observations agree with previous studies implicating osteocalcin in calcium
regulation.  For example, the chemotactic property of osteocalcin for cells
capable of resorbing bone and the specific increase in osteocalcin
synthesis by 1,25(OH)2D3, a hormone which can promote bone resorption.

This proposal will investigate the precise mechanism for the observed
defect in the decreased resorption of osteocalcin-deficient bone.  Bone
from the warfarin-treated and K-deficient rat wil be chemically
characterized for other protein alterations (analyses by 2D gels and HPLC
profiles).  The critical levels of osteocalcin and/or other Gla-containing
proteins necessary to achieve the defect will be established.  Experiments
will compare the resorption of devitalized normal and osteocalcin-deficient
bone in a model system of in vivo implant of mineralized bone particles
(BP) into subcutaneous packets.  In this model blood derived progenitor
cells differentiate into osteoclasts that resorb control bone from 5
through 28 days after implantation.  Specific cell types are identified
morphologically and resorption is quantitated by hisotomorphometric
analysis (number of multinucleated cells and percent mineralized matrix)
and biochemically (calcium content, DNA and tartrate-resistant acid
phosphatase activity).  These studies will provide information on whether
osteocalcin (or some other vitamin K-sensitive protein) is necessary for 1)
recruitment of cells to bone; 2) attachment to mineralized surfaces; 3)
promotes differentiation of a progenitor cell to a bone-resorbing cell; or
4) is involved in stimulation of activity of bone resorbing cells.  The
knowledge of cell-matrix interactions to be gained from the proposed
studies has potential applications in defining the control mechanisms of
normal bone resorption, in explaining the pathogenesis of metabolic bone
diseases, inflammatory bone destruction (peridontal disease) and in
pathogenesis and treatment of pathologic mineral deposition.

## Key facts

- **NIH application ID:** 3157067
- **Project number:** 5R01AR035166-02
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **SAM.gov UEI:** Z1L9F1MM1RY3
- **Principal Investigator:** Jane B. Lian
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $108,404
- **Award type:** 5
- **Project period:** 1986-08-01 → 1989-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3157067

## Citation

> US National Institutes of Health, RePORTER application 3157067, OSTEOCALCIN FUNCTION IN RESORPTION (5R01AR035166-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3157067. Licensed CC0.

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