• Harris, Stephen E (PI)
  • Bonewald, Linda (PI)
  • Roodman, G. David (PI)
  • Chirgwin, John (PI)
  • Yoneda, Toshiyuki (PI)
  • Mundy, Gregory (PI)

Project: Research project

Project Details


This Program Project Grant application has been initiated to develop a team
approach to clarify the mechanisms by which local factors regulate bone
remodeling, and in particular osteoclastic bone resorption. It is our
hypothesis that bone remodeling is mediated by local factors generated in
the bone and bone marrow microenvironment, and that osteoporosis results
from abnormalities in the interactions between these local factors and bone
cells. Recent studies by ourselves and others indicate that these local
factors are heterogeneous, and the complete characterization of their
effects on bone cells will require a broadly-based approach involving
investigators with expertise in widely disparate but related areas. The
specific aims of this application are: 1. To identify the specific
cellular and molecular events involved in normal osteoclastic bone
resorption, including a) the signaling mechanisms involved in osteoclast
activation; b) the expression of proteins related to osteoclast
differentiation and bone resorption; c) the activation of TGF beta during
resorption, and its regulation; 2. To determine how these cellular and
molecular mechanisms are disordered in Paget's disease. We plan to use the rapidly expanding techniques of bone cell biology,
protein chemistry and molecular biology to clarify the mechanisms by which
these local factors interact with bone cells. Since the expertise required
to identify and characterize these various mechanisms will require the
attention of investigators with different types of skills, a team approach
will be used to unite a number of diverse approaches around the tightly
focused goal of clarifying the mechanisms by which local factors regulate
normal and abnormal bone remodeling.
Effective start/end date4/1/903/31/98


  • National Institutes of Health


  • Medicine(all)


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