title: Spontaneous generation of functional osteoclasts from synovial fluid mononuclear cells as a model of inflammatory osteoclastogenesis.
abstract: In osteoimmunology, osteoclastogenesis is understood in the context of the immune system. Today, the in vitro model for osteoclastogenesis necessitates the addition of recombinant human receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). The peripheral joints of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) are characterized by an immune-mediated inflammation that can lead to bone destruction. Here, we evaluate spontaneous in vitro osteoclastogenesis in cultures of synovial fluid mononuclear cells (SFMCs) activated only in vivo. SFMCs were isolated and cultured for 21 days at 0.5-1.0 × 10(6) cells/mL in culture medium. SFMCs and healthy control peripheral blood monocytes were cultured with RANKL and M-CSF as controls. Tartrate-resistant acid phosphatase (TRAP) positive multinucleated cells were found in the SFMC cultures after 21 days. These cells expressed the osteoclast genes calcitonin receptor, cathepsin K, and integrin β3, formed lacunae on dentin plates and secreted matrix metalloproteinase 9 (MMP9) and TRAP. Adding RANKL and M-CSF potentiated this secretion. In conclusion, we show that SFMCs from inflamed peripheral joints can spontaneously develop into functionally active osteoclasts ex vivo. Our study provides a simple in vitro model for studying inflammatory osteoclastogenesis.
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.|Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Stinne R
authors.initials: SR
authors.lastname: Greisen
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Halldór Bjarki
authors.initials: HB
authors.lastname: Einarsson
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Malene
authors.initials: M
authors.lastname: Hvid
authors.affiliation: Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.|Department of Anatomy, Aarhus University, Aarhus, Denmark.
authors.forename: Ellen-Margrethe
authors.initials: EM
authors.lastname: Hauge
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.|Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Bent
authors.initials: B
authors.lastname: Deleuran
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.|Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Tue Wenzel
authors.initials: TW
authors.lastname: Kragstrup
mesh_terms: D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000503:physiopathology; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology*; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism / Q000502:physiology; D010010:Osteoclasts / Q000378:metabolism / Q000502:physiology*; D053245:RANK Ligand / Q000378:metabolism; D025241:Spondylarthritis / Q000378:metabolism / Q000503:physiopathology; D013582:Synovial Fluid / Q000378:metabolism / Q000502:physiology*
chemical_list: D053245:RANK Ligand; C505688:TNFSF11 protein, human; D016173:Macrophage Colony-Stimulating Factor
keywords: Arthritis; inflammation; osteoclast; osteoimmunology