The Sox2 high mobility group transcription factor inhibits mature osteoblast function in transgenic mice.
The Sox2 high mobility group transcription factor inhibits mature osteoblast function in transgenic mice.
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DOI：
10.1016/j.bone.2011.06.008
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发表时间：
2011-10
期刊：
影响因子：
4.1
通讯作者：
Basilico, Claudio
中科院分区：
文献类型：
--
作者：
Holmes, Greg;Bromage, Timothy G.;Basilico, Claudio
我们以前已经证明，在成骨细胞中，Sox2的表达可以被FGFs诱导，并可以抑制Wnt信号和分化。此外，在成骨细胞谱系中有条件地缺失Sox2的小鼠中，骨骼是骨量减少的，培养的成骨细胞中的Sox2失活会导致衰老表型的增殖能力丧失。为了帮助了解SOX2在成骨细胞发育中的作用，我们通过COL1α1启动子在骨中特异性地表达了SOX2，该启动子将SOX2的表达延伸到更成熟的成骨细胞。在长骨中，小梁软骨重建延迟，软骨内向皮质骨的过渡中断，导致皮质骨疏松和矿化不足。胶原沉积紊乱，破骨细胞活动模式改变。颅骨变薄，顶骨不能发育成双倍间隙。微阵列分析显示，编码非胶原性细胞外基质蛋白的各种基因显著上调或下调，其中一些成熟成骨细胞的典型基因下调。我们的研究结果表明，Sox2是体内成骨细胞成熟的负调控因子。
We have previously shown that in osteoblasts Sox2 expression can be induced by Fgfs, and can inhibit Wnt signaling and differentiation. Furthermore, in mice in which Sox2 is conditionally deleted in the osteoblastic lineage, bones are osteopenic, and Sox2 inactivation in cultured osteoblasts leads to a loss of proliferative ability with a senescent phenotype. To help understand the role of Sox2 in osteoblast development we have specifically expressed Sox2 in bone from a Col1α1 promoter, which extended Sox2 expression into more mature osteoblasts. In long bones, trabecular cartilage remodeling was delayed and the transition from endochondral to cortical bone was disrupted, resulting in porous and undermineralized cortical bone. Collagen deposition was disorganized, and patterns of osteoclast activity were altered. Calvarial bones were thinner and parietal bones failed to develop the diploic space. Microarray analysis showed significant up- or downregulation of a variety of genes coding for non-collagenous extracellular matrix proteins, with a number of genes typical of mature osteoblasts being downregulated. Our results position Sox2 as a negative regulator of osteoblast maturation in vivo.
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DOI：
10.1083/jcb.200409182
发表时间：
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期刊：
The Journal of cell biology
影响因子：
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发表时间：
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