Sox9 is required for cartilage formation
Sox9 is required for cartilage formation
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DOI：
10.1038/8792
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发表时间：
1999-05-01
期刊：
影响因子：
30.8
通讯作者：
de Crombrugghe, B
中科院分区：
文献类型：
--
作者：
Bi, WM;Deng, JM;de Crombrugghe, B
软骨发生导致软骨的形成，软骨是可以作为软骨内骨形成模板的初始骨骼元素。软骨形成开始于间充质细胞的凝聚，然后分化成软骨细胞。尽管对软骨细胞表达的终末分化产物了解很多（1-3），但对指定软骨细胞谱系的因素知之甚少（4-6）。SOX 9是一种高迁移率族（HMG）结构域转录因子，在软骨细胞和其他组织中表达（7-12）。在人类中，SOX 9单倍不足会导致先天性肢端发育不良，一种致命的骨骼畸形综合征和XY性逆转（7，13 -16）。在胚胎发生期间，Sox 9在所有软骨原基和软骨中表达，与胶原α 1（II）基因的表达一致（Col 2a 1;参考文献8、11、12），Sox 9也在其它组织中表达，包括中枢神经和泌尿生殖系统（8-12）。Sox 9与Col 2a 1和胶原蛋白α 2（XI）基因（Col 11 a2）软骨细胞特异性增强子中的必需序列结合，并可激活非软骨细胞中的这些增强子（17-19）。在这里，Sox 9被鉴定为软骨细胞谱系的调节因子。在小鼠嵌合体中，Sox 9（-/-）细胞被排除在所有软骨之外，但作为并置的间充质存在，不表达软骨细胞特异性标志物Col 2a 1、Col 9a 2、Col 11 a2和Age。这种排斥发生在软骨形成的浓缩间充质阶段，而且，在Sox 9（-/-）胚胎干（ES）细胞衍生的畸胎瘤中没有软骨发育。我们的研究结果确定Sox 9作为第一个转录因子，是软骨细胞分化和软骨形成所必需的。
Chondrogenesis results in the formation of cartilages, initial skeletal elements that can serve as templates for endochondral hone formation. Cartilage formation begins with the condensation of mesenchyme cells followed by their differentiation into chondrocytes, Although much is known about the terminal differentiation products that are expressed by chondrocytes(1-3), little is known about the factors that specify the chondrocyte lineage(4-6). SOX9 is a high-mobility-group (HMG) domain transcription factor that is expressed in chondrocytes and other tissues(7-12). In humans, SOX9 haploinsufficiency results in sues campomelic dysplasia, a lethal skeletal malformation syndrome, and XY sex reversal(7,13-16). During embryogenesis, Sox9 is expressed in all cartilage primordia and cartilages, coincident with the expression of the collagen alpha 1(II) gene (Col2a1; refs 8,11,12), Sox9 is also expressed in other tissues, including the central nervous and urogenital systems(8-12). Sox9 binds to essential sequences in the Col2a1 and collagen alpha 2(XI) gene (Col11a2) chondrocyte-specific enhancers and can activate these enhancers in non-chondrocytic cells(17-19). Here, Sox9 is identified as a regulator of the chondrocyte lineage. In mouse chimaeras, Sox9(-/-) cells are excluded from all cartilages but are present as a juxtaposed mesenchyme that does not express the chondrocyte-specific markers Col2a1, Col9a2, Col11a2 and Age. This exclusion occurred cell autonomously at the condensing mesenchyme stage of chondrogenesis, Moreover, no cartilage developed in teratomas derived from Sox9(-/-) embryonic stem (ES) cells. Our results identify Sox9 as the first transcription factor that is essential for chondrocyte differentiation and cartilage formation.