# BIOGENESIS OF EXTRACELLULAR MATRIX

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 1990 · $284,875

## Abstract

The primary goals of the work proposed here are: 1) to examine
the evolutionary history of the Type X collagen gene and to
establish its relationship to other genes encoding proteins with
collagenous domains, 2) to examine the biosynthesis of the
molecule, and its potential role in the physiological removal of
cartilage during endochondral ossification, 3) to examine the
expression of Types II and X collagens during embryonic
development and maturation of cartilage, and 4) to determine the
molecular mechanisms of the high level of expression of Type X
collagen in hypertrophic cartilage.

To accomplish these goals, we will use a combination of DNA
cloning/sequencing and protein chemistry.  Type X collagen genes
will be isolated from rat and human genomic libraries and their
structure, as determined by nucleotide sequence analysis, will be
compared to that of the chicken gene which we have isolated.

Nucleotide sequences for chicken, rat, and human Type X
collagens will be used to synthesize peptides.  These will be used
as haptens to generate specific antibodies.  Such antibodies,
together with specific DNA probes, will be used to study the
synthesis of Type X collagen and the expression of the Type X
gene during normal and abnormal cartilage development.

Isolated cDNA and genomic clones will allow studies of the
molecular mechanisms responsible for the expression of Type X
collagen by hypertrophic chondrocytes.  Nuclease hypersensitivity
and methylation in and around the Type X gene will be mapped in
expressing and non-expressing chondrocytes.  The transient
expression of the cloned genes will be studied in cultured cells,
and we will assay for the binding of nuclear proteins to sequences
within and flanking the gene.

The long term objective of these studies is to understand the
biogenesis and cellular regulation of extracellular matrices during
normal and abnormal development.  The studies on Type X
collagen should provide information about the function and
mechanisms controlling the synthesis of a specific collagen in a
connective tissue undergoing morphogenetic destruction.  They
may also provide more general insight into the synthesis of
extracellular matrix components by chondrocytes in normal
cartilage and in disease states such as rheumatoid arthritis.

## Key facts

- **NIH application ID:** 3157744
- **Project number:** 5R01AR036819-06
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **SAM.gov UEI:** JDLVAVGYJQ21
- **Principal Investigator:** BJORN REINO OLSEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $284,875
- **Award type:** 5
- **Project period:** 1985-07-01 → 1991-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3157744

## Citation

> US National Institutes of Health, RePORTER application 3157744, BIOGENESIS OF EXTRACELLULAR MATRIX (5R01AR036819-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3157744. Licensed CC0.

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