Pax2 is essential for proliferation and osteogenic differentiation of mouse mesenchymal stem cells via Runx2
Pax2 is essential for proliferation and osteogenic differentiation of mouse mesenchymal stem cells via Runx2
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Pax2 通过 Runx2 对小鼠间充质干细胞的增殖和成骨分化至关重要
DOI：
10.1016/j.yexcr.2018.08.026
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发表时间：
2018-10-15
影响因子：
3.7
通讯作者：
Ma, Junqing
中科院分区：
文献类型：
--
作者：
Lu, Mengting;Guo, Shuyu;Ma, Junqing
骨髓间充质干细胞（Mesenchymal stem cells，MSCs）是近年来再生医学领域研究的热点之一。Pax 2作为一种转录因子，是胚胎发生和肿瘤发生的主要调控因子。然而，Pax 2在骨生成中的功能尚不清楚。在这里，我们首次报道了Pax 2的表达在小鼠MSCs和骨祖细胞的成骨分化过程中逐渐增加。但在小鼠胫骨成骨细胞中，Pax 2的表达在胚胎期高于成年期。在C3 H/10/T1/2细胞和致密骨来源的小鼠骨髓间充质干细胞（mMSCs）中，Pax 2基因敲低抑制了这些细胞的增殖，下调了成骨标志基因的表达，并抑制了ALP活性和矿化。此外，Pax 2还能增强Runx 2的转录活性，激活MAPK通路中的ERK、JNK和p38基因。此外，在异位骨形成模型中，Pax 2的敲低抑制了mMSC介导的骨再生。结论：Pax 2促进小鼠骨髓间充质干细胞成骨，提示Pax 2在骨相关疾病的病理生理中发挥作用，在骨组织再生中具有潜在的应用价值。
Mesenchymal stem cells (MSCs) have been widely studied in the field of regenerative medicine with the potential to solve osteoporosis. Paired box 2 (Pax2), as a transcription factor, is the master regulator of embryogenesis and oncogenesis. However, the function of Pax2 in osteogenesis is unknown. Here, we reported for the first time that the expression of Pax2 gradually increased during osteogenic differentiation of mouse MSCs, and osteoprogenitor cells. However, detected in osteoblastic cells of mouse tibia, the expression of Pax2 in the embryonic stage was higher than that in adulthood. In C3H/10/T1/2 cells and compact bone-derived mouse MSCs (mMSCs), Pax2 knock-down inhibited the proliferation of these cells, down-regulated the expression of osteogenic marker genes, as well as repressed the ALP activity and mineralization. In addition, Pax2 enhanced the transcriptional activity of Runx2, and activated the MAPK pathway genes (ERK, JNK and p38). Furthermore, knock-down of Pax2 repressed the mMSCs-mediated bone regeneration in an ectopic bone formation model. In conclusion, Pax2 promotes osteogenesis of mouse MSCs, suggesting that Pax2 has a role in the pathophysiology of bone related diseases, and has potential application in bone tissue regeneration.