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

Journal Article · Fri Nov 17 04:00:00 EST 2006 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2006.09.076· OSTI ID:20854575

Adamopoulos, Iannis E ^[1]; Zhidao, Xia ^[2]; Lau, Y S ^[2]; Athanasou, Nicholas A ^[3]

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1. Institute of Musculoskeletal Sciences, Botnar Research Centre, Nuffield Orthopaedic Centre, University of Oxford, Oxford OX3 7LD (United Kingdom) and Department of Pathology, Nuffield Orthopaedic Centre, University of Oxford, Oxford OX3 7LD (United Kingdom)
2. Institute of Musculoskeletal Sciences, Botnar Research Centre, Nuffield Orthopaedic Centre, University of Oxford, Oxford OX3 7LD (United Kingdom)
3. Department of Pathology, Nuffield Orthopaedic Centre, University of Oxford, Oxford OX3 7LD (United Kingdom)

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{sup +} 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 {kappa}B 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.

• OSTI ID: 20854575
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 350; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACID PHOSPHATASE
ACTIN
AGING
ANTIBODIES
CELL PROLIFERATION
GROWTH FACTORS
LIGANDS
MACROPHAGES
MICE
MONOCYTES
RECEPTORS
RHEUMATIC DISEASES
SKELETON
TYROSINE