Interleukin-4 inhibition of osteoclast differentiation is stronger than that of interleukin-13 and they are equivalent for induction of osteoprotegerin production from osteoblasts
Interleukin-4 inhibition of osteoclast differentiation is stronger than that of interleukin-13 and they are equivalent for induction of osteoprotegerin production from osteoblasts
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DOI：
10.1111/j.1365-2567.2006.02538.x
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发表时间：
2007-04-01
期刊：
影响因子：
6.4
通讯作者：
Kamijo, Ryutaro
中科院分区：
文献类型：
--
作者：
Yamada, Atsushi;Takami, Masamichi;Kamijo, Ryutaro
白细胞介素（IL）-4和IL-13是密切相关的细胞因子，已知其通过靶向成骨细胞以产生抑制剂骨保护素（OPG）以及通过直接靶向破骨细胞前体来抑制破骨细胞形成。然而，它们的抑制作用是否相同仍不清楚。在含有小鼠成骨细胞和破骨细胞前体细胞的破骨细胞分化培养体系中，IL-4的抑制作用强于IL-13。这两种细胞因子诱导成骨细胞OPG的生产在类似的时间和剂量依赖性的方式。然而，IL-4在针对破骨细胞前体的直接抑制中更强。此外，在破骨细胞前体中，IL-4在比IL-13更低的浓度下诱导信号转导和转录激活因子-6（STAT 6）的磷酸化。IL-4而不是IL-13强烈抑制活化的T细胞的核因子的表达，胞质1（核因子-ATc 1），破骨细胞分化的关键因素，由这些前体。因此，IL-4和IL-13对破骨细胞前体的活性在抑制破骨细胞分化方面显示出不同，而对诱导OPG表达的成骨细胞的活性是相等的。
Interleukin (IL)-4 and IL-13 are closely related cytokines known to inhibit osteoclast formation by targeting osteoblasts to produce an inhibitor, osteoprotegerin (OPG), as well as by directly targeting osteoclast precursors. However, whether their inhibitory actions are the same remains unclear. The inhibitory effect of IL-4 was stronger than that of IL-13 in an osteoclast-differentiation culture system containing mouse osteoblasts and osteoclast precursors. Both cytokines induced OPG production by osteoblasts in similar time- and dose-dependent manners. However, IL-4 was stronger in direct inhibition that targeted osteoclast precursors. Furthermore, IL-4 induced phosphorylation of signal transducer and activator of transcription-6 (STAT6) at lower concentrations than those of IL-13 in osteoclast precursors. IL-4 but not IL-13 strongly inhibited the expression of nuclear factor of activated T-cells, cytoplasmic 1 (nuclear factor-ATc1), a key factor of osteoclast differentiation, by those precursors. Thus, the activities of IL-4 and IL-13 toward osteoclast precursors were shown to be different in regards to inhibition of osteoclast differentiation, whereas those toward osteoblasts for inducing OPG expression were equivalent.