Cellular mechanisms of osteoclast formation and lacunar resorption in giant cell granuloma of the jaw.
BACKGROUND
Giant cell granuloma (GCG) is an osteolytic tumour of the jaw which is characterised by the presence of both mononuclear and multinucleated (osteoclast-like) giant cell components. The nature of these component cells and the pathogenesis of the extensive osteolysis associated with this lesion is uncertain.


METHODS
Using cell culture techniques and immunohistochemistry, we defined the phenotypic characteristics of the mononuclear and multinucleated cells present in four cases of GCG of the jaw. We also analysed the cellular and humoral factors associated with osteoclast formation and osteolysis in these tumours and determined whether GCG stromal cells are capable of supporting osteoclast formation.


RESULTS
GCG-derived giant cells expressed the phenotypic characteristics of osteoclasts (TRAP+, VNR+, and calcitonin responsive) and were capable of lacunar resorption. In addition to macrophages, the mononuclear cell population contained numerous spindle-shaped stromal cells which proliferated in culture and expressed RANKL; these GCG-stromal cells were capable of supporting human osteoclast formation from circulating monocyte precursors.


CONCLUSIONS
Our findings indicate that the giant cells in GCG of the jaw are osteoclast-like and formed from monocyte/macrophage precursors which differentiate into osteoclasts under the influence of RANKL-expressing mononuclear stromal cells found in this lesion.
Itonaga
I
I
Nuffield Department of Orthopaedic Surgery, University of Oxford, Windmill Road, Headington, Oxford OX3 7LD, UK.
Hussein
I
I
Kudo
O
O
Sabokbar
A
A
Watt-Smith
S
S
Ferguson
D
D
Athanasou
N A
NA
D000135:Acid Phosphatase / Q000032:analysis; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001862:Bone Resorption / Q000473:pathology*; D002116:Calcitonin / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002455:Cell Division; D002648:Child; D005260:Female; D015726:Giant Cells / Q000473:pathology; D006101:Granuloma, Giant Cell / Q000473:pathology*; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D008264:Macrophages / Q000145:classification / Q000473:pathology; D008297:Male; D008336:Mandibular Diseases / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis; D010010:Osteoclasts / Q000145:classification / Q000473:pathology*; D010014:Osteolysis / Q000473:pathology; D010641:Phenotype; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D019030:Receptors, Vitronectin / Q000032:analysis; D000071681:Tartrate-Resistant Acid Phosphatase
D015415:Biomarkers; D002352:Carrier Proteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D019030:Receptors, Vitronectin; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D002116:Calcitonin; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase