title: Osteoclast formation and function in pigmented villonodular synovitis.
abstract: Pigmented villonodular synovitis (PVNS) is a synovial tumour-like lesion that frequently causes osteolysis. PVNS contains numerous macrophages and osteoclast-like giant cells. In this study, we have analysed the cytochemical and functional characteristics of mononuclear and multinucleated cells in PVNS and determined the cellular and humoral mechanisms underlying giant cell formation and resorption in PVNS. Giant cells and CD14(+) and CD14(-) mononuclear cell populations were isolated from PVNS synovial tissue and cultured alone or in the presence and absence of the osteoclastogenic factors, RANKL and M-CSF. Osteoclast formation and activity was assessed by expression of TRAP and evidence of lacunar resorption. Giant cells in PVNS expressed an osteoclast-phenotype (CD51(+) , TRAP(+) , CD14(-) , HLA-DR(-) ) and were formed only in cultures of mononuclear cells that expressed the macrophage marker CD14. Osteoclast formation required RANKL and occurred in both the presence and absence of exogenous M-CSF. CD14(-) cells in PVNS expressed RANKL. Lacunar resorption by PVNS-derived giant cells was abolished by the addition of the bisphosphonate, zoledronate. Our findings indicate that osteoclasts form by a RANKL-dependent mechanism from CD14(+) mononuclear phagocytes in PVNS. Osteoclast formation occurred even in the absence of exogenous M-CSF, a finding which is in keeping with over-expression of M-CSF playing a pathogenic role in this condition. Anti-osteoclast resorptive treatment may be useful to control osteolysis in PVNS.
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Nuffield Orthopaedic Centre, Oxford, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Taylor
authors.forename: Takesh G
authors.initials: TG
authors.lastname: Kashima
authors.forename: Helen
authors.initials: H
authors.lastname: Knowles
authors.forename: C L Max H
authors.initials: CL
authors.lastname: Gibbons
authors.forename: Duncan
authors.initials: D
authors.lastname: Whitwell
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Athanasou
mesh_terms: D000293:Adolescent; D000328:Adult; D001862:Bone Resorption / Q000209:etiology; D002478:Cells, Cultured; D005260:Female; D015726:Giant Cells / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007719:Knee Joint / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008297:Male; D010010:Osteoclasts / Q000378:metabolism / Q000502:physiology*; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013586:Synovitis, Pigmented Villonodular / Q000150:complications / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; 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