The Transcription Factor Protein Sox11 Enhances Early Osteoblast Differentiation by Facilitating Proliferation and the Survival of Mesenchymal and Osteoblast Progenitors
The Transcription Factor Protein Sox11 Enhances Early Osteoblast Differentiation by Facilitating Proliferation and the Survival of Mesenchymal and Osteoblast Progenitors
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DOI：
10.1074/jbc.m112.413377
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发表时间：
2013-08-30
影响因子：
4.8
通讯作者：
Lim, Sung-Kil
中科院分区：
文献类型：
--
作者：
Gadi, Jogeswar;Jung, Seung-Hyun;Lim, Sung-Kil
已知Sox 11缺失小鼠表现出颅面骨骼畸形、无脾以及肺、胃和胰腺发育不全的发育缺陷。尽管Sox 11在骨骼发育中的重要性，但Sox 11在骨生成中的作用尚未研究。在这项研究中，我们确定，Sox 11是一个重要的转录因子，用于调节成骨细胞前体细胞的增殖和存活，以及通过上调Tead 2的间充质祖细胞的自我更新能力。此外，Sox11还在功能性成骨细胞谱系祖细胞与骨软骨形成祖细胞的分离中起重要作用。成骨细胞系特异性转录因子Runx2和Osterix的表达增强，促进间充质细胞向成骨细胞分化。Morpholino靶向破坏斑马鱼的Sox11会损害器官形成，包括矿化不足的骨骼。这些结果表明，Sox 11通过Tead 2在间充质和成骨细胞前体的增殖和存活中起关键作用，并通过调节Runx 2和Osterix在成骨分化中起关键作用。
Sox11 deletion mice are known to exhibit developmental defects of craniofacial skeletal malformations, asplenia, and hypoplasia of the lung, stomach, and pancreas. Despite the importance of Sox11 in the developing skeleton, the role of Sox11 in osteogenesis has not been studied yet. In this study, we identified that Sox11 is an important transcription factor for regulating the proliferation and survival of osteoblast precursor cells as well as the self-renewal potency of mesenchymal progenitor cells via up-regulation of Tead2. Furthermore, Sox11 also plays an important role in the segregation of functional osteoblast lineage progenitors from osteochondrogenic progenitors. Facilitation of osteoblast differentiation from mesenchymal cells was achieved by enhanced expression of the osteoblast lineage specific transcription factors Runx2 and Osterix. Morpholino-targeted disruption of Sox11 in zebrafish impaired organogenesis, including the bones, which were under mineralized. These results indicated that Sox11 plays a crucial role in the proliferation and survival of mesenchymal and osteoblast precursors by Tead2, and osteogenic differentiation by regulating Runx2 and Osterix.