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Giant cell tumour of bone (GCTB) is a primary bone tumour that contains numerous very large, hyper-nucleated osteoclastic giant cells. Osteoclasts form from CD14+ monocytes and macrophages in the presence of receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage-colony stimulating factor (M-CSF). GCTB contains numerous growth factors, some of which have been reported to influence osteoclastogenesis and resorption. We investigated whether these growth factors are capable of substituting for M-CSF to support osteoclast formation from cultured human monocytes and whether they influence osteoclast cytomorphology and resorption. Vascular endothelial growth factor-A (VEGF-A), VEGF-D, FLT3 ligand (FL), placental growth factor (PlGF) and hepatocyte growth factor (HGF) supported RANKL-induced osteoclastogenesis in the absence of M-CSF, resulting in the formation of numerous TRAP+ multinucleated cells capable of lacunar resorption. Monocytes cultured in the presence of M-CSF, HGF, VEGF-A and RANKL together resulted in the formation of very large, hyper-nucleated (GCTB-like) osteoclasts that were hyper-resorptive. M-CSF and M-CSF substitute growth factors were identified immunohistochemically in GCTB tissue sections and these factors stimulated the resorption of osteoclasts derived from a subset of GCTBs. Our findings indicate that there are growth factors that are capable of substituting for M-CSF to induce human osteoclast formation and that these factors are present in GCTB where they influence osteoclast cytomorphology and have a role in osteoclast formation and resorption activity.

Original publication

DOI

10.1038/labinvest.2012.108

Type

Journal article

Journal

Laboratory investigation; a journal of technical methods and pathology

Publication Date

10/2012

Volume

92

Pages

1398 - 1406

Addresses

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, Nuffield Orthopaedic Centre, Oxford, UK.

Keywords

Monocytes, Osteoclasts, Giant Cells, Humans, Giant Cell Tumor of Bone, Bone Neoplasms, Bone Resorption, Acid Phosphatase, Isoenzymes, Growth Substances, Hepatocyte Growth Factor, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor D, Macrophage Colony-Stimulating Factor, Membrane Proteins, Pregnancy Proteins, RANK Ligand, Biomarkers, Tumor, Tartrate-Resistant Acid Phosphatase, Placenta Growth Factor