# CHEMISTRY AND PHYSIOLOGY OF BONE

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 1988 · $232,961

## Abstract

The long term objectives of this proposal are to investigate the
quantitative biochemistry and physiology of bone in normal and
disordered states of mineralization.  We have chosen rachitic bone
as a model of pathological bone disorders which express themselves
as a loss in bone mass (osteoporosis), undermineralization of
collagen (osteomalacia) and failure of collagen to mineralize
(rachitic bone).  We realize that these examples are quite
different from each other in etiology and causal relationships.
However, the explanation of some bone disorders on a molecular and
biochemical level will provide many insights into the structure of
hard tissues and possibly the molecular basis for some pathological
bone disorder.  Specifically we intend to determine and quantify;
1) the rate of normal bone replacement of rachitic osteoid of
vitamin D deficient animals with vitamin D3, 24R, 25(OH)2D3, 2) the
amount of new bone collagen synthesized that may mineralize or
becomes mineralized during selected periods during the rachitic
state while the animal is on a vitamin D deficient diet, 3) the
molecular locations of reducible and nonreducible intermolecular
structural cross-links in rachitic osteoid and normal bone collagen
and correlate these data with the most frequent intermolecular
distances of collagen fibrils, 4) the molecular locations of the
reducible and nonreducible structural cross-links in an almost
exclusive type I collagen containing noncalcified skeletal tissue
such as uncalcified chick leg tendon and compare it with results
from 3) above, 5) the kinetic rate of pyridinoline formation from
its cross-link precursors in normal bone collagen, rachitic osteoid
and noncalcified leg tendon by in vitro incubation studies in order
to determine the mechanism of its formation and relationship to the
three dimensional structure of collagen fibrils, and 6) the
molecular location of the cross-link histidinoalanine that
putatively links phophoprotein to collagen which only exists in the
"mineralized" portion of normal bone and to investigate if it is
present or absent in rachitic osteoid.  Rachitic chicks will be
repleted with vitamin D3, as well as with varying levels of
24R,25(OH)2,D3, and 1,25(OH)2D3 in concert and alone for ten days.
Bone will be examined biochemically for the quality of bone and
structure, (3H)Pro will be administered to vitamin D difficient 2
week-old chicks while being kept on a vitamin D deficient diet.
Bone will be taken after one, two and three weeks and biochemically
separated into mineralized and nonmineralized fraction (3H)Hyp in
the mineralized fractions will indicate amount of calcification of
D deficient state.  Normal bone collagen will be separated into its
mineralized and nonmineralized portion enzymatically. Each portion
will be digested with trypsin and the peptides separated by gel
filtration and ion-exchange chromatography.  Organic phosphorous
containing fractions will be analysed for Hyp, Hyl, and
histidinoalanine, A...

## Key facts

- **NIH application ID:** 3155084
- **Project number:** 2R01AR019969-09
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **SAM.gov UEI:** D3LHU66KBLD5
- **Principal Investigator:** GERALD MECHANIC
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $232,961
- **Award type:** 2
- **Project period:** 1979-09-10 → 1993-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155084

## Citation

> US National Institutes of Health, RePORTER application 3155084, CHEMISTRY AND PHYSIOLOGY OF BONE (2R01AR019969-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3155084. Licensed CC0.

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