Runx2 activity in committed osteoblasts is not essential for embryonic skeletogenesis.
Runx2 activity in committed osteoblasts is not essential for embryonic skeletogenesis.
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DOI：
10.3109/03008207.2014.923873
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发表时间：
2014-08
影响因子：
2.9
通讯作者：
Javed A
中科院分区：
文献类型：
--
作者：
Adhami MD;Rashid H;Chen H;Javed A
Runx 2转录因子是矿化组织发育所必需的，并且是成骨细胞定型和软骨细胞成熟所必需的。Runx 2整体缺失的小鼠表现出骨组织形成的完全失败，而软骨细胞特异性Runx 2缺陷小鼠缺乏软骨内骨化。然而，Runx 2在间充质细胞向成骨细胞谱系转化后的功能仍然未知。在这里，我们阐明了Runx 2在组织发育过程中的成骨细胞特异性要求。使用由2.3kbCol1a1启动子驱动的Cre重组酶在定向成骨细胞中缺失Runx 2。令人惊讶的是，Runx 2 ΔE8/ΔE8小鼠出生时是活的，并且基本上与野生型同窝仔没有区别。在出生时，我们未能检测到任何改变骨骼模式或程度的骨发育纯合子突变体。然而，到4周龄时，突变小鼠表现出明显的生长缺陷，体重比性别匹配的野生型同窝出生的小鼠轻20-25%。后肢的显微CT分析显示，与野生型小鼠相比，皮质骨和松质骨体积均显著减少了50%。与该观察结果一致，Runx 2 ΔE8/ΔE8小鼠四肢的骨小梁数量和厚度分别减少了51%和21%，骨小梁空间增加了2倍。除骨量采集不良外，Runx 2 ΔE8/ΔE8小鼠骨中羟基磷灰石的平均密度显著降低。总之，这些研究结果表明，在定向成骨细胞Runx 2活性的损失损害成骨细胞的功能，Runx 2是出生后，但不是胚胎软骨内骨化的关键。
Runx2 transcription factor is essential for the development of mineralized tissue, and is required for osteoblast commitment and chondrocyte maturation. Mice with global deletion of Runx2 exhibit complete failure of bone tissue formation, while chondrocyte-specific Runx2-deficient mice lack endochondral ossification. However, the function of Runx2 after commitment of mesenchymal cells to the osteoblast lineage remains unknown. Here, we elucidate the osteoblast-specific requirements of Runx2 during development of the tissue. Runx2 was deleted in committed osteoblasts using Cre-recombinase driven by the 2.3kbCol1a1 promoter. Surprisingly, Runx2ΔE8/ΔE8 mice were born alive and were essentially indistinguishable from wild-type littermates. At birth, we failed to detect any alterations in skeletal patterning or extent of bone development in homozygous mutants. However, by 4 weeks of age, mutant mice showed obvious growth deficiencies, and weighed 20–25% less than sex-matched wild-type littermates. Micro-CT analysis of the hindlimb revealed a dramatic decrease of 50% in both cortical and trabecular bone volume compared with wild-type mice. Consistent with this observation, trabecular number and thickness were decreased by 51% and 21%, respectively, and trabecular space was increased by 2-fold in limbs of Runx2ΔE8/ΔE8 mice. In addition to poor acquisition of bone mass, the average density of hydroxyapatite was markedly decreased in bone of Runx2ΔE8/ΔE8 mice. Together, these findings demonstrate that loss of Runx2 activity in committed osteoblasts impairs osteoblast function, and that Runx2 is critical for postnatal, but not embryonic endochondral ossification.
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作者：
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通讯作者：
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10.1016/j.coms.2010.05.001
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