The hematopoietic transcription factor PU.1 regulates RANK gene expression in myeloid progenitors
The hematopoietic transcription factor PU.1 regulates RANK gene expression in myeloid progenitors
复制标题
DOI：
10.1016/j.bbrc.2005.07.092
复制
发表时间：
2005-09-23
影响因子：
3.1
通讯作者：
Lee, HJ
中科院分区：
文献类型：
--
作者：
Kwon, OH;Lee, CK;Lee, HJ
破骨细胞是造血来源的骨吸收细胞。造血转录因子PU.1对破骨细胞生成至关重要;然而，PU.1调节破骨细胞生成的分子机制尚未探索。在这里，我们提出的证据表明，核因子κ B（RANK）基因的受体激活剂已被证明是破骨细胞生成的关键是PU.1的转录靶点。PU.1（-/-）祖细胞不能表达RANK基因，并且在这些细胞中PU.1的重建诱导RANK表达。用M-CSF和RANKL处理PU. 1重建细胞进一步增强了RANK基因表达。为了探讨PU.1对RANK基因表达的调控机制，我们克隆了人RANK启动子。瞬时转染试验表明，2.2 kb RANK启动子在单核细胞系RAW264.7中有功能，而PU.1的共转染在HeLa细胞中反式激活RANK启动子。综上所述，这些结果表明，PU.1调节RANK基因转录，这可能是PU.1在破骨细胞分化中的关键作用之一。(c)2005年爱思唯尔公司All rights reserved.
Osteoclasts are bone resorbing cells of hematopoietic origin. The hematopoietic transcription factor PU.1 is critical for osteoclastogenesis; however, the molecular mechanisms of PU.1 -regulated osteoclastogenesis have not been explored. Here, we present evidence that the receptor activator of nuclear factor kappa B (RANK) gene that has been shown to be crucial for osteoclastogenesis is a transcriptional target of PU.1. The PU.1(-/-) progenitor cells failed to express the RANK gene and reconstitution of PU.1 in these cells induced RANK expression. Treatment of the PU.1 reconstituted cells with M-CSF and RANKL further augmented the RANK gene expression. To explore the regulatory mechanism of the RANK gene expression by PU.1, we have cloned the human RANK promoter. Transient transfection assays have revealed that the 2.2-kb RANK promoter was functional in a monocyte line RAW264.7, whereas co-transfection of PU.1 transactivated the RANK promoter in HeLa cells. Taken together, these results suggest that PU.1 regulates the RANK gene transcription and this may represent one of the key roles of PU.1 in osteoclast differentiation. (c) 2005 Elsevier Inc. All rights reserved.