Natural killer cells trigger osteoclastogenesis and bone destruction in arthritis
| Autor: | Ulf Müller-Ladner, Emily A. Stein, Kalle Söderström, Paula Colmenero, Edgar G. Engleman, Cristina Teixeira de Matos, Ulrich Purath, Ingo H. Tarner, William H. Robinson |
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| Rok vydání: | 2009 |
| Předmět: |
musculoskeletal diseases
Macrophage colony-stimulating factor Inflammatory arthritis CD14 Osteoclasts Arthritis Biology Bone and Bones Lymphocyte Depletion Monocytes Bone remodeling Mice Neutralization Tests Osteoclast medicine Animals Humans Aged Multidisciplinary Macrophage Colony-Stimulating Factor RANK Ligand Synovial Membrane Cell Differentiation Biological Sciences Middle Aged medicine.disease Arthritis Experimental Coculture Techniques Killer Cells Natural medicine.anatomical_structure RANKL Immunology biology.protein Female Synovial membrane |
| Zdroj: | Proceedings of the National Academy of Sciences. 107:13028-13033 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1000546107 |
| Popis: | Osteoclasts are bone-eroding cells that develop from monocytic precursor cells in the presence of receptor activator of NF-κB 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. |
| Databáze: | OpenAIRE |
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