TRANSGENIC MODEL FOR GENE REGULATION IN BONE

  • Pavlin, Dubravko (PI)

Project: Research project

Project Details

Description

Mechanical stress is the dominant factor in activation of bone
remodeling, but the mechanism of its action on osteoblasts is largely
unknown. The long term goal of the studies describe this proposal is to
determine molecular mechanisms involved in transduction of mechanical
stress in bone to a biological response in osteoblasts. An in vivo model
of transgenic mice will be utilized to analyze transcriptional regulation
of the alpha1,(l) collagen (COL1A1) gene in bone cells under mechanical
stress. As the first phase of these studies, this grant focuses on
characterization of the model and comparison of changes in
histomorphometric parameters of bone formation with the endogenous COL1A1
gene activity. The periodontium of transgenic mice, harboring the COL1A1
promoter directing the expression of a reporter gene (CAT), will be
mechanically stressed by applying a defined and reproducible force on the
mandibular first molar. The response of osteoblasts covering the periodontal alveolar bone
surface will be assessed by histomorphometric measurements and
determining the mRNAs for endogenous collagen at tissue and cellular
levels. Our first specific goal is to define the magnitude of force for
optimal biological response of bone in our model. We will next identify
the type of tooth movement produced by this force to determine the
alveolar bone surfaces that will respond to applied force with bone
formation. The second goal of the study is to determine the time courses
of increase in histomorphometric measurements of bone formation and the
enhanced expression of the COL1A1 gene in periodontal osteoblasts under
mechanical stress. Quantitative measurements of the COL1A1 mRNA at the
level of tissue and in individual periodontal cells will be used as an
indicator of the endogenous collagen gene activity. The results of this study are an important prerequisite for initiation
of mapping of DNA regulatory regions and identification of nuclear
transcription factors which mediate genetic response of bone cells to
mechanical stress.
StatusFinished
Effective start/end date8/15/948/14/96

Funding

  • National Institutes of Health: $43,500.00
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Dentistry(all)

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