Runx1 dose-dependently regulates endochondral ossification during skeletal development and fracture healing.
Runx1 dose-dependently regulates endochondral ossification during skeletal development and fracture healing.
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DOI：
10.1002/jbmr.1601
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发表时间：
2012-07
影响因子：
6.2
通讯作者：
Drissi, Hicham
中科院分区：
文献类型：
--
作者：
Soung, Do Y.;Talebian, Laleh;Matheny, Christina J.;Guzzo, Rosa;Speck, Maren E.;Lieberman, Jay R.;Speck, Nancy A.;Drissi, Hicham
RUNX1在骨骼元素中表达，但其在骨折修复中的作用尚未被分析。我们创造了具有Runx1L148A亚型等位基因的小鼠，并产生了Runx1L148A/−小鼠，其中>；50%的RUNX1活性被取消。Runx1L148A/−小鼠存活，但发育不良。其生长板有明显的增殖带和肥大带，Sox9、Runx2和Runx3阳性细胞百分率下降。股骨骨折实验显示软骨骨痂形成延迟，成软骨标志物表达减少。用PRX1-CRE有条件地去除肢体间充质祖细胞中的RUNX1，未发现明显的肢体表型，但骨折后软骨性骨痂的形成延迟。当RUNX1等位基因在体外用腺病毒表达的Cre缺失时，胚胎肢芽来源的间充质细胞表现出延迟的软骨形成。综上所述，我们的数据表明，RUNX1对于软骨前体细胞向软骨细胞的定向和分化是必需的。
Runx1 is expressed in skeletal elements, but its role in fracture repair has not been analyzed. We created mice with a hypomorphic Runx1 allele (Runx1L148A) and generated Runx1L148A/− mice in which >50% of Runx1 activity was abrogated. Runx1L148A/− mice were viable but runted. Their growth plates had extended proliferating and hypertrophic zones, and the percentages of Sox9, Runx2 and Runx3 positive cells were decreased. Femoral fracture experiments revealed delayed cartilaginous callus formation and the expression of chondrogenic markers was decreased. Conditional ablation of Runx1 in the mesenchymal progenitor cells of the limb with Prx1-Cre conferred no obvious limb phenotype; however cartilaginous callus formation was delayed following fracture. Embryonic limb bud-derived mesenchymal cells showed delayed chondrogenesis when the Runx1 allele was deleted ex vivo with adenoviral-expressed Cre. Collectively, our data suggest that Runx1 is required for commitment and differentiation of chondroprogenitor cells into the chondrogenic lineage.
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影响因子：
64.8
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
通讯作者：
Speck, Nancy A.
影响因子：
10.5
作者：
Akiyama, H;Chaboissier, MC;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
4.8
作者：
Li, Z;Yan, JL;Speck, NA
通讯作者：
Speck, NA
影响因子：
--
作者：
Bradley, Elizabeth W.;Drissi, M. Hicham
通讯作者：
Drissi, M. Hicham
影响因子：
2.7
作者：
Liakhovitskaia, Anna;Lana-Elola, Eva;Medvinsky, Alexander
通讯作者：
Medvinsky, Alexander