Department of Biochemistry and Molecular Biology, Molecular Biology Section, University of Ferrara, Via Fossato di Mortara, 74, 44100, Ferrara, Italy.
Cell Mol Life Sci. 2009 Nov;66(22):3641-53. doi: 10.1007/s00018-009-0149-5. Epub 2009 Sep 11.
This study aims to define the function of Slug transcription factor in human normal osteoblasts (hOBs). To date, Slug is considered exclusively a marker of malignancy in bone tissue. Here, we identified, for the first time, a role for Slug in hOBs using a knockdown approach. We demonstrated that Slug is positively correlated with osteoblast markers, including Runx2, osteopontin, osteocalcin, Collagen type 1, Wnt/beta-catenin signaling mediators, and mineral deposition. At the same time, Slug silencing potentiates the expression of Sox-9, a factor indispensable for chondrogenic development. These data, with the finding that Slug is in vivo recruited by the promoters of Runx2 and Sox-9 genes, suggest that, in hOBs, Slug may act both as positive and negative transcriptional regulator of Runx2 and Sox-9 genes, respectively. In summary, our results support the hypothesis that Slug functions as a novel regulator of osteoblast activity and may be considered a new factor required for osteoblast maturation.
本研究旨在确定 slug 转录因子在人正常成骨细胞（hOBs）中的功能。迄今为止，slug 被认为是骨组织恶性肿瘤的唯一标志物。在这里，我们首次通过敲低方法鉴定了 slug 在 hOBs 中的作用。我们证明 slug 与成骨细胞标志物呈正相关，包括 Runx2、骨桥蛋白、骨钙素、胶原 1 型、Wnt/β-catenin 信号转导介质和矿物质沉积。同时，Slug 沉默增强了 Sox-9 的表达，Sox-9 是软骨发生所必需的因子。这些数据以及发现 Slug 在体内被 Runx2 和 Sox-9 基因启动子募集的事实表明，在 hOBs 中，Slug 可能分别作为 Runx2 和 Sox-9 基因的正和负转录调节剂发挥作用。总之，我们的结果支持 Slug 作为成骨细胞活性的新型调节因子的假说，并且可以被认为是成骨细胞成熟所必需的新因子。
