REGULATION OF OSTEOBLAST SPECIFIC GENE EXPRESSION

Project: Research project

Project Details

Description

Osteoporosis is defined as a rapid reduction in bone mass. With the
growing longevity of the population, there is a substantial increase in
the frequency of this disorder. Bones are in a constant state of
remodeling which consists of two processes: bone resorption and bone
formation, performed by the osteoclasts and osteoblasts, respectively.
With age, the thickness of the born gradually declines, primarly because
the osteoblasts are unable to keep pace with the osteoclasts.
Determining the key regulatory mechanisms involved in maintaining the
integrity of the osteoblast is important for understanding the aging
process. This is a proposal to investigate the control of osteoblast-specific
gene expression. A novel molecular/genetic experimental system will be
utilized to investigate the regulation of four osteoblastic genes:
estrogen receptor, bone Gla protein, matrix Gla protein and
liver/bone/kidney alkaline phosphatase. A set of intertypic hybrids
will be constructed between highly differentiated rat osteosarcomas and
human fibroblasts. Genetic studies of this nature have been utilized to
identify tissue-specific trans-dominant negative regulatory elements
termed extinguishers in a number of experimental system. The goal of this project will be to identify and localize extinguishers
which control the expression of osteoblast-specific genes. In addition,
experiments are designed to identify the Cis sequences in the
osteooblast-specific structural gene that are required for their
regulation. By identifying and ultimately isolating these unique
regulators, we can begin to understand their role in the development and
maintenance of the osteoblast. Important insights can be gained into
perturbations of these regulatory circuits which might occur in the
osteoblast during aging.
StatusFinished
Effective start/end date7/1/916/30/97

Funding

  • National Institutes of Health
  • National Institutes of Health: $81,518.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $94,247.00

ASJC

  • Medicine(all)

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