title: CD14- mononuclear stromal cells support (CD14+) monocyte-osteoclast differentiation in aneurysmal bone cyst.
abstract: Aneurysmal bone cyst (ABC) is a benign osteolytic bone lesion in which there are blood-filled spaces separated by fibrous septa containing giant cells. The nature of the giant cells in this lesion and the mechanism of bone destruction in ABC is not certain. In this study, we have analysed several characteristics of mononuclear and multinucleated cells in the ABC and examined the cellular and molecular mechanisms of ABC osteolysis. The antigenic and functional phenotype of giant cells in ABC was determined by histochemistry/immunohistochemistry using antibodies to macrophage and osteoclast markers. Giant cells and CD14+ and CD14- mononuclear cells were isolated from ABC specimens and cultured on dentine slices and coverslips with receptor activator of nuclear factor κB ligand (RANKL)+/- macrophage-colony stimulating factor (M-CSF) and functional and cytochemical evidence of osteoclast differentiation sought. Giant cells in ABC expressed an osteoclast-like phenotype (CD51+, CD14-, cathepsin K+, TRAP+) and were capable of lacunar resorption, which was inhibited by zoledronate, calcitonin and osteoprotegerin (OPG). When cultured with RANKL±M-CSF, CD14+, but not CD14-, mononuclear cells differentiated into TRAP+ multinucleated cells that were capable of lacunar resorption. M-CSF was not necessary for osteoclast formation from CD14+ cell cultures. CD14- cells variably expressed RANKL, OPG and M-CSF but supported osteoclast differentiation. Our findings show that the giant cells in ABC express an osteoclast-like phenotype and are formed from CD14+ macrophage precursors. CD14- mononuclear stromal cells express osteoclastogenic factors and most likely interact with CD14+ cells to form osteoclast-like giant cells by a RANKL-dependent mechanism.
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Nuffield Orthopaedic Centre, Oxford, UK.
authors.forename: Richard Mi
authors.initials: RM
authors.lastname: Taylor
authors.forename: Takeshi G
authors.initials: TG
authors.lastname: Kashima
authors.forename: Francesca K E
authors.initials: FK
authors.lastname: Hemingway
authors.forename: Arundhati
authors.initials: A
authors.lastname: Dongre
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Knowles
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Athanasou
mesh_terms: D000293:Adolescent; D000328:Adult; D017824:Bone Cysts, Aneurysmal / Q000473:pathology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D005260:Female; D015726:Giant Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D010010:Osteoclasts / Q000473:pathology*; D053244:Osteoprotegerin / Q000378:metabolism; D010641:Phenotype; D053245:RANK Ligand / Q000378:metabolism; D055815:Young Adult
chemical_list: D018950:Lipopolysaccharide Receptors; D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D016173:Macrophage Colony-Stimulating Factor