Runx2/Cbfa1 stimulates transdifferentiation of primary skeletal myoblasts into a mineralizing osteoblastic phenotype
Runx2/Cbfa1 stimulates transdifferentiation of primary skeletal myoblasts into a mineralizing osteoblastic phenotype
复制标题
DOI：
10.1016/j.yexcr.2004.07.031
复制
发表时间：
2004-11-01
影响因子：
3.7
通讯作者：
García, AJ
中科院分区：
文献类型：
--
作者：
Gersbach, CA;Byers, BA;García, AJ
Runx2是骨形态发生蛋白（BMP）信号下游的转录激活因子，对成骨细胞分化和骨形成和维持至关重要。bmp激活复杂的信号网络，利用多种信号分子和转录因子诱导间充质细胞类型成骨细胞标志物的表达。然而，Runx2在这一过程中的作用，特别是在独立于bmp调节的其他调控元件的环境中，仍然知之甚少。在本研究中，我们使用逆转录病毒基因传递来检测Runx2在原代成肌细胞中持续表达的影响。通过抑制MyoD和myogenin mRNA水平以及减少肌管形成，Runx2可以抑制肌生成。此外，runx2刺激成骨包括成骨细胞基因表达、碱性磷酸酶活性和生物矿物沉积。值得注意的是，这些成骨标志物的诱导水平明显高于bmp -2处理的对照组。这些结果表明，Runx2转录因子的直接外源表达，仅是BMP信号的众多下游靶点之一，足以诱导肌源性细胞转分化为矿化成骨谱系。这项工作强调了Runx2作为成骨和细胞分化调节剂的效力，并为间充质细胞的可塑性提供了新的见解。(C) 2004爱思唯尔公司版权所有。
Runx2, a transcriptional activator downstream of bone morphogenetic protein (BMP) signaling, is essential to osteoblastic differentiation and bone formation and maintenance. BMPs activate complex signaling networks, utilizing numerous signaling molecules and transcription factors to induce expression of osteoblastic markers in mesenchymal cell types. However, the role of Runx2 in this process, particularly in an environment independent of the other regulatory elements modulated by BMPs, remains poorly understood. In the present study, we used retroviral gene delivery to examine the effects of sustained Runx2 expression in primary myoblasts. Runx2 inhibited myogenesis, as demonstrated by suppression of MyoD and myogenin mRNA levels and reduced myotube formation. Additionally, Runx2-stimulated osteogenesis including ostcoblastic gene expression, alkaline phosphatase activity, and biological mineral deposition. Notably, these osteogenic markers were induced to significantly greater levels than those observed in BMP-2-treated controls. These results demonstrate that direct exogenous expression of the Runx2 transcription factor, only one of numerous downstream targets of BMP signaling, is sufficient to induce transdifferentiation of myogenic cells into a mineralizing osteogenic lineage. This work underscores the potency of Runx2 as a regulator of osteogenesis and cell differentiation and provides new insights into the plasticity of committed mesenchymal cells. (C) 2004 Elsevier Inc. All rights reserved.