Targeting extracellular signal-regulated kinase (ERK) signaling has therapeutic implications for inflammatory osteolysis

Sung Wook Seo, Daniel Lee, Hiroshi Minematsu, Abraham D. Kim, Mike Shin, Samuel K. Cho, Dae Won Kim, Jay Yang, Francis Y. Lee

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

The extracellular signal-regulated kinase 1/2 (ERK) pathway, part of the mitogen-activated protein kinase (MAPK) family, is well-known for its role in cell differentiation and proliferation. In the context of osteoclastogenesis, macrophage colony stimulating factor (M-CSF) is an upstream activator of ERK signals for the survival of osteoclast precursors prior to their differentiation into multinucleated osteoclasts. In this study, we demonstrate by using both in vivo and in vitro models that the ERK signaling pathway involves an inflammatory response of various cells mediating osteolysis. Osteoblasts exhibit innate immune response by expressing M-CSF in response to lipopolysaccharide (LPS). LPS induced M-CSF expression is mediated by ERK. The inhibition of ERK signaling attenuated the inflammatory response to LPS both in vivo and in vitro. Thus, the ERK pathway may be a potentially important therapeutic target in the treatment of inflammatory osteolysis.

Original languageEnglish
Pages (from-to)695-702
Number of pages8
JournalBone
Volume46
Issue number3
DOIs
StatePublished - Mar 2010
Externally publishedYes

Keywords

  • Extracellular signal-regulated kinase (ERK) signaling
  • Inflammatory osteolysis
  • Lipopolysaccharide (LPS)
  • Macrophage-colony stimulating factor (M-CSF)
  • Osteoblasts

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