Enhancement of RANKL-induced MITF-E expression and osteoclastogenesis by TGF-β
Enhancement of RANKL-induced MITF-E expression and osteoclastogenesis by TGF-β
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DOI：
10.1002/cbf.3028
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发表时间：
2014-07-01
影响因子：
3.6
通讯作者：
Murakami, Masaru
中科院分区：
文献类型：
--
作者：
Asai, Kumiko;Funaba, Masayuki;Murakami, Masaru
小眼症相关转录因子（MITF）是一种在有限类型的细胞（包括破骨细胞）中表达的转录因子，但MITF在破骨细胞生成过程中的表达和作用尚未完全阐明。在RAW 264.7细胞和原代骨髓细胞中，NF-κ B配体受体激活剂（RANKL）对破骨细胞的分化刺激诱导了MITF-E亚型的表达，但未诱导MITF-A亚型的表达。RANKL诱导的抗酒石酸酸性磷酸酶（TRAP）阳性多核细胞的形成在表达MITF-E siRNA的RAW 264. 7细胞中受到抑制。转化生长因子-β（TGF-β）增强RANKL诱导的MITF-E表达和TRAP阳性多核细胞形成。特别是，TGF-β增强了较大破骨细胞的形成。在RANKL存在下，TGF-β同时增强了与破骨细胞发育和活性相关的基因NFATc 1、TRAP和CtsK的表达水平。此外，树突状细胞特异性跨膜蛋白（DC-STAMP），Itgav，Itga 2，Itga 5，Itgb 1，Itgb 3和Itgb 5，细胞粘附和融合相关基因的表达上调与TGF-β共处理。特别是，Itgav和Itgb 5对RANKL（含或不含TGF-β）的调节表达与MITF-E相似。由于MITF参与某些细胞系统中的细胞融合，因此这些结果暗示MITF-E作为破骨细胞生成增强剂的作用，并且通过TGF-β处理增强RANKL诱导的MITF-E mRNA和MITF依赖性基因表达水平。版权所有（C）2014约翰威利父子有限公司
Microphthalmia-associated transcription factor (MITF) is a transcription factor that is expressed in limited types of cells, including osteoclasts, but the expression and role of MITF during osteoclastogenesis have not been fully elucidated. The expression of the MITF-E isoform but not that of the MITF-A isoform was induced in response to differentiation stimulation towards osteoclasts by receptor activator of NF-kappa B ligand (RANKL) in both RAW264.7 cells and primary bone marrow cells. The RANKL-induced formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells was inhibited in RAW264.7 cells expressing siRNA for MITF-E. Transforming growth factor-beta (TGF-beta) enhanced RANKL-induced MITF-E expression and - TRAP positive multinucleated cell formation. In particular, TGF-beta potentiated the formation of larger osteoclasts. The expression levels of NFATc1, TRAP and CtsK, genes related to osteoclast development and activity, were concurrently enhanced by TGF-beta in the presence of RANKL. Furthermore, the expression of dendritic cell-specific transmembrane protein (DC-STAMP), Itgav, Itga2, Itga5, Itgb1, Itgb3 and Itgb5, genes related to cell adhesion and fusion, were up-regulated by co-treatment with TGF-beta. In particular, the regulatory expression of Itgav and Itgb5 in response to RANKL with or without TGF-beta resembled that of MITF-E. Because MITF is involved in cell fusion in some cell systems, these results imply a role for MITF-E as an enhancer of osteoclastogenesis and that RANKL-induced levels of both MITF-E mRNA and of MITF-dependent gene expression are enhanced by treatment with TGF-beta. Copyright (C) 2014 John Wiley & Sons, Ltd.