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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 kappaB 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 publication

DOI

10.1016/j.bbrc.2006.09.076

Type

Journal article

Journal

Biochemical and biophysical research communications

Publication Date

11/2006

Volume

350

Pages

478 - 483

Addresses

Institute of Musculoskeletal Sciences, Botnar Research Centre, Nuffield Orthopaedic Centre, University of Oxford, Oxford OX3 7LD, UK. iadamopoulos@path.wustl.edu

Keywords

Leukocytes, Mononuclear, Monocytes, Osteoclasts, Humans, Bone Resorption, Hepatocyte Growth Factor, Macrophage Colony-Stimulating Factor, Flow Cytometry, Cell Proliferation, Cell Survival, Adult, Male, Proto-Oncogene Proteins c-met, RANK Ligand