Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06034, USA.
J Bone Miner Res. 2012 Jul;27(7):1585-97. doi: 10.1002/jbmr.1601.
Runx1 is expressed in skeletal elements, but its role in fracture repair has not been analyzed. We created mice with a hypomorphic Runx1 allele (Runx1(L148A) ) and generated Runx1(L148A/-) mice in which >50% of Runx1 activity was abrogated. Runx1(L148A/-) 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.
Runx1 在骨骼元素中表达，但它在骨折修复中的作用尚未被分析。我们创建了具有低功能 Runx1 等位基因（Runx1(L148A)）的小鼠，并生成了 >50% Runx1 活性被消除的 Runx1(L148A/-)小鼠。Runx1(L148A/-) 小鼠具有活力但体型矮小。它们的生长板有延长的增殖和肥大区， Sox9、Runx2 和 Runx3 阳性细胞的百分比减少。股骨骨折实验显示软骨性愈伤组织形成延迟，软骨生成标志物的表达减少。用 Prx1-Cre 在肢体的间充质祖细胞中条件性剔除 Runx1 并没有赋予明显的肢体表型；然而，骨折后软骨愈伤组织的形成被延迟。胚胎肢芽衍生的间充质细胞在体外使用腺病毒表达的 Cre 剔除 Runx1 等位基因时，软骨发生延迟。总之，我们的数据表明 Runx1 是软骨祖细胞向软骨谱系的分化所必需的。
