# OSTEOINDUCTION AND THE BIOLOGY OF BONE GROWTH FACTORS

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 1993 · $254,230

## Abstract

This project seeks to define the role of the recently cloned factor,
osteogenic protein-1 (OP-1), in bone cell biology.  OP-1 and other bone
morphogenetic proteins (BMP's) are homologous members of the TGF-beta
superfamily of growth and differentiation factors which were originally
isolated from demineralized bone powder.  These proteins are strongly
implicated as the key regulatory elements in the pathway of osteoblastic
differentiation leading to osteoinductive bone formation.  Osteoinduction
is a developmental process in which bone tissue forms de novo by
recruitment and commitment of relatively undifferentiated mesenchymal
cells.  Osteoinduction occurs naturally in skeletal development of the
embryo or fetus, and it may be partially recapitulated in fracture
healing, surgical repair of bone, and osteointegration of prosthetic
devices and implants.  Abnormal operation of the osteoinductive
differentiation cascade may explain the pathophysiology of numerous
skeletal disorders such as osteoporosis.  We hypothesize that OP-1
induces new bone tissue by recruiting mesenchymal precursor cells to the
osteoblastic pathway, and by stimulating osteoblastic phenotypic
expression in committed cells.  the major aim of this project is to
characterize the regulatory effects of recombinant OP-1 on the osteoblast
in vitro.  Human and rat primary osteoblasts (and other osteoblastic and
undifferentiated cell lines) will be used to examine OP-1 regulation of
proliferation and expression of phenotypic markers (osteocalcin, alkaline
phosphatase, mineralization, etc.).  Methods include Northern analysis
of mRNA levels, radioimmunoassay of osteocalcin, immunohistochemistry,
in situ hybridization, and regulation of osteocalcin promoter-CAT
constructs in ROS 17/2.8 cells.  The second aim is to evaluate the role
of OP-1 in the recruitment and commitment of mesenchymal cells to the
osteoblastic phenotype.  Mesenchymal cells from developing osteoinductive
implants and limb buds will be exposed to OP-1 under various conditions.
Shell-less chick embryos in vitro will be implanted with OP-1 in
methylcellulose discs at different times and locations.  Target cells for
OP-1 will be labeled with 125I-OP-1 and visualized autoradiographically.
The third aim is to characterize the mechanism of OP-1 osteoinduction,
including matrix and cell surface receptor binding of OP-1, latent OP-1
activation and clearance, and synergism/antagonism of OP-1 biological
activity by other bone-related polypeptide growth factors.  These studies
will proceed in vivo with rat implants and in vitro with osteoblasts,
determining whether OP-1 enhances osteoblastic expression directly, or
acts through secondary paracrine factors.  OP-1 is produced at low levels
in bone and at high levels in kidney.  Thus the mechanism by which the
mineralized extracellular matrix sequesters and presents OP-1 to bone
cells is critical to the understanding of bone cell biology as it relates
to skeletal development, maintenan...

## Key facts

- **NIH application ID:** 3158507
- **Project number:** 2R01AR038349-06A1
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **SAM.gov UEI:** Z1L9F1MM1RY3
- **Principal Investigator:** Peter V Hauschka
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $254,230
- **Award type:** 2
- **Project period:** 1987-05-01 → 1997-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158507

## Citation

> US National Institutes of Health, RePORTER application 3158507, OSTEOINDUCTION AND THE BIOLOGY OF BONE GROWTH FACTORS (2R01AR038349-06A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158507. Licensed CC0.

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