Hepatocyte growth factor can substitute for M-CSF to support osteoclastogenesis

Iannis Adamopoulos, Zhidao Xia, Yu Sin Lau, Nicholas A. Athanasou

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Osteopetrotic mice lacking functional macrophage-colony stimulating factor (M-CSF) recover with ageing, suggesting that alternative osteoclastogenesis pathways exist. Hepatocyte growth factor (HGF) and M-CSF signal through tyrosine kinase receptors and phosphorylate common transducers and effectors such as Src, Grb2, and PI3-Kinase. HGF is known to play a role in osteoclast formation, and in this study we have determined whether HGF could replace M-CSF to support human osteoclastogenesis. We found that the HGF receptor, c-Met, is expressed by the CD14+ monocyte fraction of human peripheral blood mononuclear cells (PBMC). HGF was able to support monocyte-osteoclast differentiation in the presence of receptor activator for nuclear factor κB ligand as evidenced by the formation of numerous multinucleated tartrate-resistant acid phosphatase and vitronectin receptor positive cells which formed F-actin rings and were capable of lacunar resorption. The addition of a neutralising antibody to M-CSF did not inhibit osteoclast differentiation. HGF is a well-established survival factor and viability assays and live/dead staining showed that it promoted the survival and proliferation of monocytes and osteoclasts in a manner similar to M-CSF. Our findings indicate that HGF can substitute for M-CSF to support human osteoclast formation.

Original languageEnglish (US)
Pages (from-to)478-483
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume350
Issue number2
DOIs
StatePublished - Nov 17 2006
Externally publishedYes

Keywords

  • Bone resorption
  • Hepatocyte growth factor
  • Osteoclasts
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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