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Role of Cell-matrix Interactions in Osteoclast Differentiation

  • Kevin P. McHugh
  • Zhenxin Shen
  • Tania Crotti
  • M. R. Flannery
  • Roberto Jose Fajardo
  • Benjamin E. Bierbaum
  • Steven R. Goldring
Part of the Advances in Experimental Medicine and Biology book series (volume 602)

Osteoclast and their mononuclear cell precursors are present within the bone microenvironment at sites of physiologic and pathologic bone resorption. Analysis of tissues from sites of bone resorption reveal that cells expressing the full morphological and functional properties of mature osteoclasts are restricted to the immediate bone surface. We hypothesize that in addition to cytokines, components of the bone matrix and specific cell surface receptors on osteoclasts and their precursors play an essential role in determining the genetic profile and functional properties of fully differentiated resorbing osteoclasts. We have employed expression profiling, with an in vitro model of matrix-dependent osteoclast differentiation, to identify the molecular pathways by which bone matrix-interactions induce terminal osteoclast differentiation and activation. In preliminary studies, we have identified unique genes and transcriptional pathways that are induced by interaction of osteoclast precursors with specific components of the mineralized bone matrix. The authenticity of the gene profiles, as markers of osteoclast differentiation and activation, have been provisionally validated using an in vivo animal bone implantation model and by examination of tissues from patients with specific forms of pathologic osteoclast-mediated bone resorption. The ultimate goal of our studies is to identify new molecular targets for inhibiting osteoclast-mediated bone loss in disorders of pathologic bone loss.

Keywords

Bone Resorption Osteoclast Differentiation Tartrate Resistant Acid Phosphatase Osteoclast Precursor Calcitonin Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Kevin P. McHugh
    • 1
  • Zhenxin Shen
    • 1
  • Tania Crotti
    • 1
  • M. R. Flannery
    • 1
  • Roberto Jose Fajardo
    • 1
  • Benjamin E. Bierbaum
    • 1
  • Steven R. Goldring
    • 1
  1. 1.New England Baptist Bone and Joint InstituteHarvard Medical SchoolBostonUSA

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