MafB negatively regulates RANKL-mediated osteoclast differentiation
MafB negatively regulates RANKL-mediated osteoclast differentiation
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DOI：
10.1182/blood-2006-09-048249
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发表时间：
2007-04-15
期刊：
影响因子：
20.3
通讯作者：
Kim, Nacksung
中科院分区：
文献类型：
--
作者：
Kim, Kabsun;Kim, Jung Ha;Kim, Nacksung
核因子 kappa B 配体受体激活剂 (RANKL) 通过调节各种转录因子诱导造血细胞形成破骨细胞。在这里，我们发现 MafB 负向调节 RANKL 诱导的破骨细胞分化。在破骨细胞生成过程中，RANKL 显着降低 MafB 的表达水平。骨髓源性单核/巨噬细胞谱系细胞 (BMM) 中 MafB 的过表达会抑制 TRAP(+) 多核破骨细胞的形成，但保留 BMM 的吞噬活性。此外，BMM 中 MafB 的过度表达会减弱 RANKL 介导的破骨细胞生成过程中 NFATc1 和破骨细胞相关受体 (OSCAR) 的基因诱导。此外，MafB 蛋白干扰 c-Fos、Mitf 和 NFATc1 的 DNA 结合能力，抑制它们对 NFATc1 和 OSCAR 的反式激活。此外，RNAi 减少 MafB 的表达可增强破骨细胞生成并增加 NFATc1 和 OSCAR 的表达。综上所述，我们的结果表明 MafB 可以作为 RANKL 介导的破骨细胞生成的重要调节剂。
Receptor activator of nuclear factor kappa B ligand (RANKL) induces osteoclast formation from hematopoietic cells via regulation of various transcription factors. Here, we show that MafB negatively regulates RANKL-induced osteoclast differentiation. Expression levels of MafB are significantly reduced by RANKL during osteoclastogenesis. Overexpression of MafB in bone marrow-derived monocyte/macrophage lineage cells (BMMs) inhibits the formation of TRAP(+) multinuclear osteoclasts, but phagocytic activity of BMMs is retained. Furthermore, overexpression of MafB in BMMs attenuates the gene induction of NFATc1 and osteoclast-associated receptor (OSCAR) during RANKL-mediated osteoclastogenesis. In addition, MafB proteins interfere with the DNA-binding ability of c-Fos, Mitf, and NFATc1, inhibiting their transactivation of NFATc1 and OSCAR. Furthermore, reduced expression of MafB by RNAi enhances osteoclastogenesis and increases expression of NFATc1 and OSCAR. Taken together, our results suggest that MafB can act as an important modulator of RANKL-mediated osteoclastogenesis.