EFFECTS OF ESTROGEN ON OSTEOCLASTS FROM TRANSGENIC MICE

Project: Research project

Description

Little information is available on factors directly controlling the
osteoclast or the molecular events responsible for osteoclast formation and
bone resorption. The cell and molecular biological characterization of the
osteoclast has been severely hampered by the inability to isolate large
numbers of osteoclasts or osteoclast precursors and the unavailability of
established osteoclastic cell lines. The proposed studies are designed to
allow the establishment of cell lines that express the full differentiated
phenotype of osteoclasts from osteoclast tumors formed in transgenic mice.
These cell lines will then be used to address questions concerning the
effects of estrogen and other osteotropic factors on osteoclast function. The proposed strategy involves directing the expression of an oncogene,
such as SV40 Tantigen, specifically or preferentially to osteoclast cells
using the regulatory regions of the genes encoding tartrate resistant acid
phosphatase (TRAP) and the calcitonin receptor (CTR). Transgenic mice
expressing these hybrid transgenes are expected to develop bone tumors of
osteoclast origin, or possibly immortalized osteoclast precursors in the
blood, spleen or bone marrow. These immortalized cells will be placed in
culture and cell lines will be established. The cell lines will be
extensively characterized to determine the extent to which they resemble
osteoclasts or osteoclast precursors and to test their ability to
differentiate in culture. In addition, cell lines will be derived from
both male and female mice to allow a comparison of phenotype. Finally, since estrogen may affect the formation and activity of
osteoclasts, studies will be undertaken to determine the effects of
estrogen on the growth and differentiation of these cells and on their
ability to resorb bone. In addition, estrogen will be administered to the
transgenic mice to determine if the pattern of mononuclear or
multinucleated osteoclastic cells is altered in vivo. Based on the success of the transgenic mouse approach for deriving
established differentiated cell lines representing other rare cell types,
we are hopeful that the proposed studies will lead to the development of
established cell lines representing osteoclasts or osteoclast precursors.
Such cell lines would provide a novel system for in vitro analysis of
important questions concerning the role of estrogen and other osteotropic
factors or accessory cells in regulating osteoclast function.
StatusFinished
Effective start/end date9/30/916/30/11

Funding

  • National Institutes of Health
  • National Institutes of Health: $286,713.00
  • National Institutes of Health: $256,441.00
  • National Institutes of Health: $230,676.00
  • National Institutes of Health: $175,599.00
  • National Institutes of Health
  • National Institutes of Health: $269,540.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $157,848.00
  • National Institutes of Health: $256,458.00
  • National Institutes of Health: $242,627.00
  • National Institutes of Health: $236,562.00
  • National Institutes of Health
  • National Institutes of Health: $261,708.00
  • National Institutes of Health: $248,869.00
  • National Institutes of Health: $207,729.00

Fingerprint

Osteoclasts
Transgenic Mice
Estrogens
Cell Line
Cytoskeleton
Genes
Viral Tumor Antigens
Bone and Bones
Bone Marrow
Macrophage Colony-Stimulating Factor
Organized Financing
T-Lymphocytes
Polyomavirus Transforming Antigens
Disintegrins
Phenotype
Metalloproteases

ASJC

  • Medicine(all)