title: Hepatocyte growth factor can substitute for M-CSF to support osteoclastogenesis.
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 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.
authors.affiliation: Institute of Musculoskeletal Sciences, Botnar Research Centre, Nuffield Orthopaedic Centre, University of Oxford, Oxford OX3 7LD, UK. iadamopoulos@path.wustl.edu
authors.forename: Iannis E
authors.initials: IE
authors.lastname: Adamopoulos
authors.forename: Zhidao
authors.initials: Z
authors.lastname: Xia
authors.forename: Yu Sin
authors.initials: YS
authors.lastname: Lau
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Athanasou
mesh_terms: D000328:Adult; D001862:Bone Resorption; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology*; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis; D053245:RANK Ligand / Q000494:pharmacology
chemical_list: D053245:RANK Ligand; D017228:Hepatocyte Growth Factor; D016173:Macrophage Colony-Stimulating Factor; D019859:Proto-Oncogene Proteins c-met