Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, PR China.
Department of Medical Genetics, Nanjing Medical University, Longmian Road 101, Nanjing 211166, PR China.
Exp Cell Res. 2018 Oct 15;371(2):342-352. doi: 10.1016/j.yexcr.2018.08.026. Epub 2018 Aug 23.
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.
间充质干细胞（MSCs）在再生医学领域得到了广泛研究，具有解决骨质疏松症的潜力。配对盒 2（Pax2）作为一种转录因子，是胚胎发生和致癌作用的主要调节因子。然而，Pax2 在成骨中的功能尚不清楚。在这里，我们首次报道 Pax2 的表达在小鼠 MSCs 和成骨前体细胞的成骨分化过程中逐渐增加。然而，在小鼠胫骨的成骨细胞中，胚胎期的 Pax2 表达高于成年期。在 C3H/10/T1/2 细胞和致密骨来源的小鼠 MSCs（mMSCs）中，Pax2 敲低抑制了这些细胞的增殖，下调了成骨标记基因的表达，并抑制了 ALP 活性和矿化。此外，Pax2 增强了 Runx2 的转录活性，并激活了 MAPK 通路基因（ERK、JNK 和 p38）。此外，Pax2 敲低抑制了 mMSCs 在异位骨形成模型中的骨再生。总之，Pax2 促进了小鼠 MSCs 的成骨作用，表明 Pax2 在骨相关疾病的病理生理学中具有作用，并具有在骨组织再生中的潜在应用。
