Interferon-γ directly inhibits TRANCE-induced osteoclastogenesis
Interferon-γ directly inhibits TRANCE-induced osteoclastogenesis
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DOI：
10.1006/bbrc.2000.3577
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发表时间：
2000-10-05
影响因子：
3.1
通讯作者：
Chambers, TJ
中科院分区：
文献类型：
--
作者：
Fox, SW;Chambers, TJ
免疫系统对骨重塑具有深远的影响。 IFN-γ是免疫细胞的主要产物，可有效抑制骨吸收，但其作用机制尚不清楚。我们在无基质的单核前体细胞培养物中发现，IFN-γ以剂量依赖性方式强烈抑制TRANCE/RANKL诱导的破骨细胞形成。这种对破骨细胞祖细胞的直接影响并不是由于 IFN-γ 刺激 NO 产生，因为 NOS 抑制剂 1400W 和 L-NAME 无法逆转这种抑制。然而，TGF beta(1) 在多种细胞功能上与 IFN-γ 具有相反的作用，能够拮抗 IFN-γ 的作用。这表明IFN-γ通过主动引导破骨细胞祖细胞向破骨细胞的替代杀细胞谱系分化来防止破骨细胞形成。 (C) 2000 年学术出版社。
The immune system has profound effects on bone remodeling. IFN-gamma, a major product of immune cells, potently inhibits bone resorption, but its mechanism of action is unknown, We found in cultures of stroma-free mononuclear precursors that IFN-gamma strongly suppresses TRANCE/RANKL-induced osteoclast formation in a dose-dependent manner. This direct effect on osteoclast progenitors was not due to stimulation of NO production by IFN-gamma, as the NOS inhibitors 1400W and L-NAME were unable to reverse the suppression. However, TGF beta(1), which has opposing actions to IFN-gamma on diverse cellular functions, was able to antagonize the effect of IFN-gamma. This suggests that IFN-gamma prevents osteoclast formation by actively directing the differentiation of osteoclastic progenitors toward an alternative cytocidal lineage to the osteoclast. (C) 2000 Academic Press.