Dipartimento di Biochimica e Biologia Molecolare, Università degli Studi di Ferrara, Via Fossato di Mortara, Ferrara, Italy.
Exp Cell Res. 2011 May 1;317(8):1159-68. doi: 10.1016/j.yexcr.2010.12.011. Epub 2010 Dec 21.
CXCL12/CXCR4 chemokine/receptor axis signaling has recently been found to play an important role in the remodeling of bone tissue, but little is known about the molecular mechanisms that are involved. The present study shows that CXCL12 is present at high levels both in human mesenchymal stem cells (hMSCs) and primary osteoblasts (hOBs). When osteogenesis was induced, CXCL12 expression was strictly confined to mineralized nodules. To investigate what mechanisms contribute to the maintenance of a correct expression of CXCL12 in bone cellular context, we analyzed the relationship between CXCL12 and Slug, a transcription factor recently associated with osteoblast maturation. By gene silencing and chromatin immunoprecipitation assay, we showed that both proteins are required for the mineralization process and CXCL12 is transcriptionally and functionally regulated by Slug, which is recruited at specific sites to its gene promoter in vivo. These findings showed for the first time a positive correlation between CXCL12 signaling and Slug activity, thus corroborating the role of these two proteins in bone cellular context and suggesting a new potential target for bone tissue repair and regeneration.
CXCL12/CXCR4 趋化因子/受体轴信号通路最近被发现对骨组织重塑起着重要作用，但其中涉及的分子机制还知之甚少。本研究表明，CXCL12 在人骨髓间充质干细胞（hMSCs）和原代成骨细胞（hOBs）中均高表达。成骨诱导时，CXCL12 表达严格局限于矿化结节。为了研究哪些机制有助于在骨细胞环境中维持 CXCL12 的正确表达，我们分析了 CXCL12 与 Slug 之间的关系，Slug 是最近与成骨细胞成熟相关的转录因子。通过基因沉默和染色质免疫沉淀分析，我们表明这两种蛋白都需要矿化过程，Slug 转录并在功能上调节 CXCL12，Slug 可在体内募集到其基因启动子的特定部位。这些发现首次显示 CXCL12 信号与 Slug 活性之间存在正相关，从而证实了这两种蛋白在骨细胞环境中的作用，并为骨组织修复和再生提供了一个新的潜在靶点。
