Signal transducer and activator of transcription 3 (Stat3) is a cytoplasmic transcription factor that participates in various biologic processes. Loss of Stat3 causes hyperimmunoglobulin E syndrome, presenting with skeletal disorders including osteoporosis, recurrent fractures, scoliosis, and craniosynostosis. The objective of this study is to explore the effect and mechanism of Stat3 on osteogenesis of mesenchymal progenitors. Stat3 was conditionally knockout (CKO) in mesenchymal progenitors by crossing the pair-related homeobox gene 1-cre (Prx1-Cre) with Stat3-floxed strain mice. Whole-mount-skeletal staining, histology, and micro-CT were used to assess the differences between Stat3 CKO and control mice. Further, in vitro experiments were conducted to evaluate the osteogenesis potential of primary isolated bone marrow mesenchymal stem cells (BMSCs) from both control and Stat3 CKO mice. After osteogenic induction for 14d, alizarin red staining was used to show the calcium deposit, while the western blotting was applied to detect the expression of osteogenic markers. Compared with the control, Stat3 CKO mice were present with shortened limbs, multiple fractures of long bone, and open calvarial fontanels. The abnormal growth plate structure and reduced collagen fiber were found in Stat3 CKO limbs. According to micro-CT analysis, the reduced cortical bone thickness and bone volume were found on Stat3 CKO mice. The in vitro osteogenic differentiation of BMSCs was inhibited in Stat3 CKO samples. After osteogenic induction for 14d, the significantly diminished calcium deposits were found in Stat3 CKO BMSCs. The decreased expression of osteogenic markers (OPN and COL1A1) was observed in Stat3 CKO BMSCs, compared with the control. Stat3 played a critical role in bone development and osteogenesis. Loss of Stat3 impaired the osteogenesis of mesenchymal progenitors in vivo and in vitro.

中文翻译：

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信号转导和转录激活因子 3 的缺失损害了体内和体外间充质祖细胞的成骨

信号转导和转录激活因子 3 (Stat3) 是一种参与各种生物过程的细胞质转录因子。Stat3 的缺失会导致高免疫球蛋白 E 综合征，表现为骨骼疾病，包括骨质疏松症、复发性骨折、脊柱侧弯和颅缝早闭。本研究的目的是探讨Stat3对间充质祖细胞成骨的影响和机制。通过将配对相关同源框基因 1-cre (Prx1-Cre) 与 Stat3-floxed 品系小鼠杂交，Stat3 在间充质祖细胞中被有条件地敲除 (CKO)。使用整体骨骼染色、组织学和显微 CT 来评估 Stat3 CKO 和对照小鼠之间的差异。更远，进行体外实验以评估来自对照和 Stat3 CKO 小鼠的原代分离的骨髓间充质干细胞 (BMSC) 的成骨潜力。成骨诱导14d后，茜素红染色显示钙沉积，Western blotting检测成骨标志物的表达。与对照相比，Stat3 CKO 小鼠出现四肢缩短、长骨多处骨折和开放的颅骨囟门。在Stat3 CKO肢体中发现异常生长板结构和减少的胶原纤维。根据显微 CT 分析，在 Stat3 CKO 小鼠上发现皮质骨厚度和骨量减少。在 Stat3 CKO 样品中，BMSCs 的体外成骨分化受到抑制。成骨诱导14d后，在 Stat3 CKO BMSC 中发现钙沉积显着减少。与对照相比，在 Stat3 CKO BMSC 中观察到成骨标志物（OPN 和 COL1A1）的表达降低。Stat3 在骨骼发育和成骨过程中发挥了关键作用。Stat3 的缺失损害了体内和体外间充质祖细胞的成骨。