FoxA family members are crucial regulators of the hypertrophic chondrocyte differentiation program.
FoxA family members are crucial regulators of the hypertrophic chondrocyte differentiation program.
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DOI：
10.1016/j.devcel.2012.03.011
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发表时间：
2012-05-15
影响因子：
11.8
通讯作者：
Lassar, Andrew B.
中科院分区：
文献类型：
--
作者：
Ionescu, Andreia;Kozhemyakina, Elena;Nicolae, Claudia;Kaestner, Klaus H.;Olsen, Bjorn R.;Lassar, Andrew B.
在软骨内骨化过程中，小的未成熟软骨细胞增大形成肥大软骨细胞，表达胶原蛋白 X。在这项工作中，我们证明 FoxA 因子在软骨形成过程中被诱导，与胶原蛋白 X 增强剂中的保守结合位点结合，并可以促进软骨细胞和成纤维细胞中胶原蛋白 X 荧光素酶报告基因的表达。此外，我们通过功能获得和丧失分析证明，FoxA 因子在驱动内源性胶原蛋白 X 和其他肥大软骨细胞特异性基因的表达方面发挥着至关重要的作用。软骨细胞中缺乏 FoxA2 和 FoxA3 表达的转基因小鼠表现出软骨细胞肥大、碱性磷酸酶表达和胸骨矿化方面的缺陷，此外还表现出出生后侏儒症，这与其生长板中胶原蛋白 X 和 MMP13 表达显着降低有关。总之，我们的研究结果表明 FoxA 家族成员是肥大软骨细胞分化程序的关键调节因子。
During endochondral ossification small immature chondrocytes enlarge to form hypertrophic chondrocytes, which express collagen X. In this work, we demonstrate that FoxA factors are induced during chondrogenesis, bind to conserved binding sites in the collagen X enhancer, and can promote the expression of a collagen X-luciferase reporter in both chondrocytes and fibroblasts. In addition, we demonstrate by both gain and loss of function analyses that FoxA factors play a crucial role driving the expression of both endogenous collagen X and other hypertrophic chondrocyte-specific genes. Mice engineered to lack expression of both FoxA2 and FoxA3 in their chondrocytes display defects in chondrocyte hypertrophy, alkaline phosphatase expression, and mineralization in their sternebrae and in addition exhibit postnatal dwarfism that is coupled to significantly decreased expression of both collagen X and MMP13 in their growth plates. Together, our findings indicate that FoxA family members are crucial regulators of the hypertrophic chondrocyte differentiation program.
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影响因子：
4
作者：
Kaestner, Klaus H.
通讯作者：
Kaestner, Klaus H.
影响因子：
1.2
作者：
Besnard, V;Wert, SE;Whitsett, JA
通讯作者：
Whitsett, JA
影响因子：
2.7
作者：
Guo, J;Chung, UI;Kronenberg, HM
通讯作者：
Kronenberg, HM
影响因子：
11.8
作者：
Arnold, Michael A.;Kim, Yuri;Olson, Eric N.
通讯作者：
Olson, Eric N.
DOI：
10.1073/pnas.0504750102
发表时间：
2005-10-11
影响因子：
11.1
作者：
Akiyama, H;Kim, JE;de Crombrugghe, B
通讯作者：
de Crombrugghe, B