Natural killer cells trigger osteoclastogenesis and bone destruction in arthritis
Natural killer cells trigger osteoclastogenesis and bone destruction in arthritis
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DOI：
10.1073/pnas.1000546107
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发表时间：
2010-07-20
影响因子：
11.1
通讯作者：
Engleman, Edgar G.
中科院分区：
文献类型：
--
作者：
Soederstroem, Kalle;Stein, Emily;Engleman, Edgar G.
破骨细胞是在NF-κ B配体受体激活因子（RANKL）和巨噬细胞集落刺激因子（M-CSF）存在下从单核细胞前体细胞发育而来的骨侵蚀细胞。破骨细胞对于生理性骨重建是必不可少的，但局部破骨细胞过度活性是导致关节周围骨破坏的原因，这是类风湿性关节炎（RA）患者的特征性表现。类风湿关节炎骨侵蚀部位破骨细胞的起源尚不清楚。自然杀伤（NK）细胞以及单核细胞在RA患者的炎症关节中大量存在。我们在此发现，这种NK细胞同时表达RANKL和M-CSF，并且经常与RA滑膜中的CD 14（+）单核细胞相关。此外，当滑膜NK细胞与单核细胞在体外共培养时，它们触发它们分化成破骨细胞，这是一个依赖于RANKL和M-CSF的过程。与RA一样，胶原诱导性关节炎（CIA）小鼠关节中的NK细胞表达RANKL。在诱导CIA之前消耗小鼠的NK细胞可以降低随后关节炎的严重程度，几乎完全防止骨质侵蚀。这些结果表明NK细胞可能在与炎症性关节炎相关的骨骼破坏中发挥重要作用。
Osteoclasts are bone-eroding cells that develop from monocytic precursor cells in the presence of receptor activator of NF-kappa B 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.