title: Natural killer cells trigger osteoclastogenesis and bone destruction in arthritis.
abstract: Osteoclasts are bone-eroding cells that develop from monocytic precursor cells in the presence of receptor activator of NF-kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Osteoclasts are essential for physiological bone remodeling, but localized excessive osteoclast activity is responsible for the periarticular bone destruction that characteristically occurs in patients with rheumatoid arthritis (RA). The origin of osteoclasts at sites of bone erosion in RA is unknown. Natural killer (NK) cells, as well as monocytes, are abundant in the inflamed joints of patients with RA. We show here that such NK cells express both RANKL and M-CSF and are frequently associated with CD14(+) monocytes in the RA synovium. Moreover, when synovial NK cells are cocultured with monocytes in vitro, they trigger their differentiation into osteoclasts, a process dependent on RANKL and M-CSF. As in RA, NK cells in the joints of mice with collagen-induced arthritis (CIA) express RANKL. Depletion of NK cells from mice before the induction of CIA reduces the severity of subsequent arthritis and almost completely prevents bone erosion. These results suggest that NK cells may play an important role in the destruction of bone associated with inflammatory arthritis.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Palo Alto, CA 94304, USA. kallesuchi@gmail.com
authors.forename: Kalle
authors.initials: K
authors.lastname: Söderström
authors.forename: Emily
authors.initials: E
authors.lastname: Stein
authors.forename: Paula
authors.initials: P
authors.lastname: Colmenero
authors.forename: Ulrich
authors.initials: U
authors.lastname: Purath
authors.forename: Ulf
authors.initials: U
authors.lastname: Müller-Ladner
authors.forename: Cristina Teixeira
authors.initials: CT
authors.lastname: de Matos
authors.forename: Ingo H
authors.initials: IH
authors.lastname: Tarner
authors.forename: William H
authors.initials: WH
authors.lastname: Robinson
authors.forename: Edgar G
authors.initials: EG
authors.lastname: Engleman
mesh_terms: D000368:Aged; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology*; D001842:Bone and Bones / Q000276:immunology / Q000473:pathology*; D002454:Cell Differentiation / Q000276:immunology; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008212:Lymphocyte Depletion; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology; D009500:Neutralization Tests; D010010:Osteoclasts / Q000276:immunology / Q000473:pathology*; D053245:RANK Ligand / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology
chemical_list: D053245:RANK Ligand; D016173:Macrophage Colony-Stimulating Factor