Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Osteogenic Differentiation by Modulating AMPK/ULK1-Dependent Autophagy
Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Osteogenic Differentiation by Modulating AMPK/ULK1-Dependent Autophagy
复制标题
线粒体磷酸烯醇丙酮酸羧激酶通过调节 AMPK/ULK1 依赖性自噬调节成骨分化
DOI：
10.1002/stem.3091
复制
发表时间：
2019-12-01
期刊：
影响因子：
5.2
通讯作者：
Zhou, Yongsheng
中科院分区：
文献类型：
--
作者：
Li, Zheng;Liu, Xuenan;Zhou, Yongsheng
线粒体磷酸烯醇丙酮酸羧激酶（PCK2）是一种限速酶，在多种生理过程中发挥重要作用。PCK2失代偿导致各种能量代谢紊乱。然而，关于PCK2对人间充质干细胞（hMSCs）成骨的影响，我们知之甚少。在这里，我们报告了PCK2作为MSCs成骨分化的积极调节因子的新功能。除了在合成代谢中众所周知的作用外，我们还证明PCK2调节自噬。PCK2缺乏显著抑制自噬，导致MSCs成骨能力受损。另一方面，PCK2过表达可促进细胞自噬；这伴随着MSCs成骨分化的增加。此外，PCK2通过amp活化蛋白激酶(AMPK)/unc-51样自噬激活激酶1（ULK1）依赖性自噬调节MSCs的成骨分化。总的来说，我们目前的研究揭示了PCK2在整合自噬和骨形成中的新作用，为基于干细胞的骨组织工程提供了一个潜在的靶点，可能会导致代谢性骨病的治疗方法的改进。茎Cells2019;37:1542 - 1555
Mitochondrial phosphoenolpyruvate carboxykinase (PCK2) is a rate-limiting enzyme that plays critical roles in multiple physiological processes. The decompensation of PCK2 leads to various energy metabolic disorders. However, little is known regarding the effects of PCK2 on osteogenesis by human mesenchymal stem cells (hMSCs). Here, we report a novel function of PCK2 as a positive regulator of MSCs osteogenic differentiation. In addition to its well-known role in anabolism, we demonstrate that PCK2 regulates autophagy. PCK2 deficiency significantly suppressed autophagy, leading to the impairment of osteogenic capacity of MSCs. On the other hand, autophagy was promoted by PCK2 overexpression; this was accompanied by increased osteogenic differentiation of MSCs. Moreover, PCK2 regulated osteogenic differentiation of MSCs via AMP-activated protein kinase (AMPK)/unc-51 like autophagy activating kinase 1(ULK1)-dependent autophagy. Collectively, our present study unveiled a novel role for PCK2 in integrating autophagy and bone formation, providing a potential target for stem cell-based bone tissue engineering that may lead to improved therapies for metabolic bone diseases.Stem Cells2019;37:1542-1555