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

Research output: Chapter in Book/Report/Conference proceedingConference contribution

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Title of host publicationOsteoimmunology
Pages107-111
Number of pages5
DOIs
StatePublished - Dec 1 2007

Publication series

NameAdvances in Experimental Medicine and Biology
Volume602
ISSN (Print)0065-2598

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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