BIX01294 suppresses osteoclast differentiation on mouse macrophage-like Raw264.7 cells
BIX01294 suppresses osteoclast differentiation on mouse macrophage-like Raw264.7 cells
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DOI：
10.17305/bjbms.2013.2339
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发表时间：
2013-11-01
影响因子：
3.4
通讯作者：
Suzuki, Naoto
中科院分区：
文献类型：
--
作者：
Tsuda, Hiromasa;Zhao, Ning;Suzuki, Naoto
基因表达受包括组蛋白甲基化在内的表观遗传机制控制。破骨细胞是一种骨吸收细胞，通过核因子-kappa B配体受体激活剂（RANKL）刺激从造血前体细胞分化而来。虽然BIX01294是G9a的特异性抑制剂，其作为组蛋白H3赖氨酸9（H3K9）甲基转移酶起作用，据报道改变细胞分化阶段，但其对破骨细胞分化的影响尚不清楚。在这项研究中，BIX01294对破骨细胞分化的影响进行了检查。在这里，我们发现BIX01294剂量依赖性地减少RANKL诱导的抗酒石酸酸性磷酸酶阳性多核破骨细胞样细胞从鼠巨噬细胞样Raw 264.7细胞的分化。在分化过程中，BIX01294处理仅使RANKL单独刺激的细胞的生长速率降低不到14%。此外，蛋白质印迹分析表明，BIX01294减少RANKL诱导的碳酸酐酶II和组织蛋白酶K的产生，并减少RANKL诱导的活化T细胞c1的核因子，一种主要的调节转录因子，在破骨细胞分化过程中的产生。这些结果表明BIX01294抑制RANKL诱导的破骨细胞分化。这是首次报道BIX01294对破骨细胞分化的影响。(C)2013 FB & H基础医学科学协会版权所有
Gene expressionis controlled by epigenetic mechanisms including histone methylation. Osteoclasts are bone-resorptive cells that differentiate from hematopoietic-precursor cells by receptor activator of nuclear factor-kappa B ligand (RANKL) stimulation. Although BIX01294, a specific inhibitor of G9a, which works as a histone H3 lysine 9 (H3K9) methyltransferase, reportedly changes cellular differentiational stage, its effect on osteoclast differentiation is unclear. In this study, the effects of BIX01294 on osteoclast differentiation were examined. Here, we showed that BIX01294 dose-dependently reduced RANKL-induced tartrate-resistant acid phosphatase positive multinuclear osteoclast-like cell differentiation from murine macrophage-like Raw264.7 cells. During differentiation, growth rates reduced only less than 14% of those of cells stimulated with RANKL alone by BIX01294 treatment. Moreover, western blot analysis showed that BIX01294 reduced RANKL-induced carbonic anhydrase II and cathepsin K production and decreased RANKL-induced nuclear factor of activated T-cell c1, a master regulatory transcription factor, production during osteoclast differentiation. These results suggest that BIX01294 suppresses RANKL-induced osteoclast differentiation. This is the first report about the effect of BIX01294 on osteoclast differentiation. (C) 2013 Association of Basic Medical Sciences of FB&H. All rights reserved