Molecular mechanism of basic calcium phosphate crystal-induced activation of human fibroblasts: Role of nuclear factor κB, activator protein 1, and protein kinase C

Geraldine M. McCarthy, James A. Augustine, Albert S. Baldwin, Pamela A. Christopherson, Herman S. Cheung, Pamela R. Westfall, Robert I. Scheinman

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Synovial fluid basic calcium phosphate (BCP) crystals are markers of severe joint degeneration in osteoarthritis. BCP crystals cause mitogenesis of articular cells and stimulate matrix metalloprotease production, thus promoting degradation of articular tissues. Previous work suggested that BCP crystal-induced cell activation required intracellular crystal dissolution, induction of proto-oncogene expression, and activation of signal transduction pathways involving protein kinase C and mitogen-activated protein kinases. Here we further elucidate the mechanisms of BCP crystal-induced cell activation as BCP crystals activate transcription factors nuclear factor κB and activator protein I in human fibroblasts. We confirm the role of protein kinase C in BCP crystal-induced mitogenesis in human fibroblasts. In contrast, we demonstrate that BCP crystals do not activate signal transduction pathways involving protein tyrosine kinases or phosphatidylinositol 3-kinase. These data further define the mechanism of cell activation by BCP crystals and confirm its selectivity, an observation that may have therapeutic implications.

Original languageEnglish (US)
Pages (from-to)35161-35169
Number of pages9
JournalJournal of Biological Chemistry
Volume273
Issue number52
DOIs
StatePublished - Dec 25 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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