# IN VITRO INITIATION OF BIOLOGICAL CALCIFICATION

> **NIH NIH R01** · HOSPITAL FOR SPECIAL SURGERY · 1990 · $128,967

## Abstract

Cartilage calcification is an essential step in the processes of
fracture healing and bone growth (endochondral ossification).
The goal of the proposed studies is to determine the ways in
which cartilage calcification is regulated.  Since mammals and
birds demonstrate different patterns of cartilage calcification
they provide excellent models for examining these regulatory
process.  Mammalian and avian cartilage calcification can be
differentially modeled in vitro using a well developed model of
chondrogenesis.  Chondrogenesis (cartilage formation) occurs in
vitro when mesenchymal cells (isolated from embryonic limb
buds) are cultured at high density in media containing 1 mM
calcium:  the matrix will calcify in the presence of 3-4 mM
inorganic phosphate.  The long range goal of the proposed study
is to use chick and mouse mesenchymal cell systems to
characterize events in initial calcification.  Chemical analyses,
light and electron microscopy, x-ray diffraction and infra-red
spectroscopy, and immunochemistry will be used to evaluate the
mineralized matrix formed in vitro.  Experiments are designed
initially to optimize the culture conditions to provide maximal
"physiologic" matrix mineralization by varying a) ascorbic acid,
b) phosphate, c) beta-glycerol phosphate, d) calcium, e) fetal calf
serum, and f) atmospheric conditions.  The calcified tissue
formed in the avian and murine cell culture systems will be
compared to each other and to mineralized cartilage produced in
vivo, with respect to:  a) type of matrix undergoing
mineralization, b) mineral characteristics, and c) cells regulating
the mineralization process.  The cultured cells will than be
chemically or physically modified in order to test the hypothesis
that viable, as opposed to necrotic, cells are responsible for
mineralization.  The effect of alteration of matrix properties on
mineralization will be examined by using agents that alter:  a)
cartilage differentiation and development (BrDU and vitamin A),
b) proteoglycan synthesis, composition and/or properties (vitamin
A, xylosides, hyaluronidase, polylysine), and c) synthesis of other
extracellular matrix proteins (cAMP).  The culture systems will
be examined to determine how clinically relevant trace elements
(F, A1, Fe, Ga, Ti, V, Ni, Cr and Co) control the extent of cell
mediated mineralization.  These cell culture studies are unique
due to their emphases on the mechanism of cell-mediated
calcification.  Their clinical significance comes from the basic
information on calcification mechanisms they will provide as
well as from the specific data they will generate on the effect of
certain therapies on these mechanisms.

## Key facts

- **NIH application ID:** 3158280
- **Project number:** 5R01AR037661-04
- **Recipient organization:** HOSPITAL FOR SPECIAL SURGERY
- **Principal Investigator:** ADELE L BOSKEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $128,967
- **Award type:** 5
- **Project period:** 1987-08-01 → 1992-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158280

## Citation

> US National Institutes of Health, RePORTER application 3158280, IN VITRO INITIATION OF BIOLOGICAL CALCIFICATION (5R01AR037661-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158280. Licensed CC0.

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