The Hidden Curriculum of an English for Academic Purposes Reform in Chinese Universities
The Hidden Curriculum of an English for Academic Purposes Reform in Chinese Universities
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Schnurri-3通过Runx2和VEGF调节BMP9诱导的人羊膜间充质干细胞的成骨分化和血管生成
DOI：
10.1038/s41419-020-2279-5
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发表时间：
2020-06-01
影响因子：
1
通讯作者：
Li, Yulong
中科院分区：
文献类型：
--
作者：
Li, Yulong
人羊膜间充质干细胞(HAMSCs)是一种多潜能的前体细胞，可分化为不同的细胞系(成骨细胞、软骨细胞和脂肪细胞)，具有良好的血管生成能力。SchNurri-3(Shn3)是与果蝇Shn相关的一个大的锌指蛋白，是出生后骨形成的关键介质。骨形态发生蛋白9(BMP9)是最有效的成骨BMP之一，能强烈上调MSCs中多种成骨和血管生成相关因子的表达。目前尚不清楚Shn3如何参与BMP9诱导的hAMSCs成骨分化和血管生成。在本研究中，我们进行了一项全面的研究，以确定Shn3在BMP9诱导的hAMSCs成骨分化和血管生成中的作用，并分析相关的信号通路。体外和体内实验结果表明，Shn3显著抑制BMP9诱导的hAMSCs的早期和晚期成骨分化、成骨相关因子的表达以及hAMSCs在裸鼠皮下异位成骨。Shn3还抑制BMP9诱导的小鼠血管生成分化、血管生成相关因子的表达和皮下血管侵袭。从机制上，我们发现Shn3显著抑制BMP9的表达和BMP/Smad和BMP/MAPK信号通路的激活。此外，我们还进一步发现了矮小相关转录因子2(Runx2)、血管内皮生长因子(VEGF)以及BMP和Shn3信号通路共享的靶基因的活性。沉默Shn3可以显著增强Runx2的表达，Runx2直接调节下游靶血管内皮生长因子，从而将成骨分化与血管生成结合起来。综上所述，我们的研究结果表明，Shn3显著抑制BMP9诱导的hAMSCs的成骨分化和血管生成。Shn3的作用主要是通过抑制BMP/Smad信号通路和直接调节血管生成血管内皮生长因子的Runx2的表达来实现的。中国高等教育面临的根本挑战是其官僚治理体系；然而，经过几次改革，它仍然没有受到影响。上海最近的EAP政策并没有挑战这一制度，相反，它指责普通英语课程未能为学生的学业做好准备。通过对以往研究数据的批判性反思，本研究发现，新的EAP课程和取代普通英语课程的政策隐藏着一个隐藏的课程，该课程加强了对知识的控制，使现有的高等教育系统合法化，并再现了未来的学术劣势。上海的EAP政策是政策制定者作为新中产阶级成员以及他们的帮凶--新自由主义和新保守派--社会流动性斗争的结果。然而，阻力和冲突存在于每个工作环境中，包括上海EAP的环境，正如本研究所证明的那样，尽管一些学生和教师的抵制会适得其反。
Human amniotic mesenchymal stem cells (hAMSCs) are multiple potent progenitor cells (MPCs) that can differentiate into different lineages (osteogenic, chondrogenic, and adipogenic cells) and have a favorable capacity for angiogenesis. Schnurri-3 (Shn3) is a large zinc finger protein related to Drosophila Shn, which is a critical mediator of postnatal bone formation. Bone morphogenetic protein 9 (BMP9), one of the most potent osteogenic BMPs, can strongly upregulate various osteogenesis- and angiogenesis-related factors in MSCs. It remains unclear how Shn3 is involved in BMP9-induced osteogenic differentiation coupled with angiogenesis in hAMSCs. In this investigation, we conducted a comprehensive study to identify the effect of Shn3 on BMP9-induced osteogenic differentiation and angiogenesis in hAMSCs and analyze the responsible signaling pathway. The results from in vitro and in vivo experimentation show that Shn3 notably inhibits BMP9-induced early and late osteogenic differentiation of hAMSCs, expression of osteogenesis-related factors, and subcutaneous ectopic bone formation from hAMSCs in nude mice. Shn3 also inhibited BMP9-induced angiogenic differentiation, expression of angiogenesis-related factors, and subcutaneous vascular invasion in mice. Mechanistically, we found that Shn3 prominently inhibited the expression of BMP9 and activation of the BMP/Smad and BMP/MAPK signaling pathways. In addition, we further found activity on runt-related transcription factor 2 (Runx2), vascular endothelial growth factor (VEGF), and the target genes shared by BMP and Shn3 signaling pathways. Silencing Shn3 could dramatically enhance the expression of Runx2, which directly regulates the downstream target VEGF to couple osteogenic differentiation with angiogenesis. To summarize, our findings suggested that Shn3 significantly inhibited the BMP9-induced osteogenic differentiation and angiogenesis in hAMSCs. The effect of Shn3 was primarily seen through inhibition of the BMP/Smad signaling pathway and depressed expression of Runx2, which directly regulates VEGF, which couples BMP9-induced osteogenic differentiation with angiogenesis.The fundamental challenge in China's higher education is its bureaucratic governance system; however, it remains untouched after several reforms. The recent Shanghai EAP policy does nothing to challenge the system, but rather, it blames the general English curriculum for failing to prepare students academically. By critically reflect on data from some previous studies, this study discovered that the new EAP curriculum and the policy proposed to replace the general English curriculum harboured a hidden curriculum that tightened the control of knowledge, legitimizing the existing higher education system, and reproducing future academic subalterns. This Shanghai EAP policy is the result of the policymakers' social mobility struggle as members of a new middle class, together with their accomplices: neoliberalism and neoconservatives. However, resistance and conflict exist in every working context, including the context of Shanghai EAP as justified in the study, despite some of the students' and the teacher's resistance being counter-productive.