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首页> 外文期刊>Journal of Cellular Physiology >Inhibitory regulation of osteoclast differentiation by interleukin-3 via regulation of c-Fos and Id protein expression
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Inhibitory regulation of osteoclast differentiation by interleukin-3 via regulation of c-Fos and Id protein expression

机译:抑制破骨细胞的监管分化interleukin-3通过监管蛋白表达c-Fos和Id

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摘要

Interleukin-3 (IL-3) is produced under various pathological conditions and is thought to be involved in the pathogenesis of inflammatory diseases; however, its function in bone homeostasis under normal conditions or nature of the downstream molecular targets remains unknown. Here we examined the effect of IL-3 on osteoclast differentiation from mouse and human bone marrow-derived macrophages (BMMs). Although IL-3 can induce osteoclast differentiation of multiple myeloma bone marrow cells, IL-3 greatly inhibited osteoclast differentiation of human BMMs isolated from healthy donors. These inhibitory effects of IL-3 were only observed at early time points (days 0 and 1). IL-3 inhibited the expression of c-Fos and NFATc1 in BMMs treated with RANKL. However, IL-3-mediated inhibition of osteoclast differentiation was not completely reversed by ectopic expression of c-Fos or NFATc1. Importantly, IL-3 induced inhibitor of DNA binding/differentiation (Id)1 in hBMMs, while Id2 were sustained during osteoclast differentiation of mBMMs treated with IL-3. Ectopic expression of NFATc1 in Id2-deficient BMMs completely reversed the inhibitory effect of IL-3 on osteoclast differentiation. Furthermore, inflammation-induced bone erosion was markedly inhibited by IL-3 administration. Taken together, our results suggest that IL-3 plays an inhibitory role in osteoclast differentiation by regulating c-Fos and Ids, and also exerts anti-bone erosion effects.
机译:Interleukin-3 (IL-3)是产生在不同病理条件和被认为是参与炎症的发病机制疾病;体内平衡在正常情况下或性质下游分子靶点仍然未知。我们检查了IL-3对破骨细胞的影响从老鼠和人类骨分化骨髓来源的巨噬细胞(桥梁养护管理系统)。可以诱导破骨细胞分化的多吗骨髓瘤骨髓细胞,IL-3大大抑制破骨细胞分化人类桥梁养护管理系统的孤立从健康的捐赠者。IL-3只观察到早期的时间点(天0和1),IL-3抑制的表达c-Fos桥梁养护管理系统和NFATc1 RANKL对待。然而,IL-3-mediated抑制破骨细胞分化不完全逆转异位表达c-Fos或NFATc1。重要的是,IL-3抑制剂诱导的DNA在hBMMs绑定/分化(Id) 1,而Id2破骨细胞分化过程中持续吗mBMMs IL-3对待。在Id2-deficient NFATc1桥梁养护管理系统完全逆转IL-3在破骨细胞的抑制作用分化。inflammation-induced骨侵蚀是明显的被IL-3管理。我们的研究结果表明,IL-3起到了抑制破骨细胞分化的调节作用c-Fos和id,并施加anti-bone侵蚀效果。

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