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Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Osteogenic Differentiation by Modulating AMPK/ULK1‐Dependent Autophagy
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 mese...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916635/ https://www.ncbi.nlm.nih.gov/pubmed/31574189 http://dx.doi.org/10.1002/stem.3091 |
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author | Li, Zheng Liu, Xuenan Zhu, Yuan Du, Yangge Liu, Xuejiao Lv, Longwei Zhang, Xiao Liu, Yunsong Zhang, Ping Zhou, Yongsheng |
author_facet | Li, Zheng Liu, Xuenan Zhu, Yuan Du, Yangge Liu, Xuejiao Lv, Longwei Zhang, Xiao Liu, Yunsong Zhang, Ping Zhou, Yongsheng |
author_sort | Li, Zheng |
collection | PubMed |
description | 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 cells 2019;37:1542–1555 |
format | Online Article Text |
id | pubmed-6916635 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69166352019-12-23 Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Osteogenic Differentiation by Modulating AMPK/ULK1‐Dependent Autophagy Li, Zheng Liu, Xuenan Zhu, Yuan Du, Yangge Liu, Xuejiao Lv, Longwei Zhang, Xiao Liu, Yunsong Zhang, Ping Zhou, Yongsheng Stem Cells Stem Cell Technology: Epigenetics, Genomics, Proteomics, and Metabonomics 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 cells 2019;37:1542–1555 John Wiley & Sons, Inc. 2019-10-14 2019-12 /pmc/articles/PMC6916635/ /pubmed/31574189 http://dx.doi.org/10.1002/stem.3091 Text en ©2019 The Authors. stem cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2019 This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Stem Cell Technology: Epigenetics, Genomics, Proteomics, and Metabonomics Li, Zheng Liu, Xuenan Zhu, Yuan Du, Yangge Liu, Xuejiao Lv, Longwei Zhang, Xiao Liu, Yunsong Zhang, Ping Zhou, Yongsheng Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Osteogenic Differentiation by Modulating AMPK/ULK1‐Dependent Autophagy |
title | Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Osteogenic Differentiation by Modulating AMPK/ULK1‐Dependent Autophagy |
title_full | Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Osteogenic Differentiation by Modulating AMPK/ULK1‐Dependent Autophagy |
title_fullStr | Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Osteogenic Differentiation by Modulating AMPK/ULK1‐Dependent Autophagy |
title_full_unstemmed | Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Osteogenic Differentiation by Modulating AMPK/ULK1‐Dependent Autophagy |
title_short | Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Osteogenic Differentiation by Modulating AMPK/ULK1‐Dependent Autophagy |
title_sort | mitochondrial phosphoenolpyruvate carboxykinase regulates osteogenic differentiation by modulating ampk/ulk1‐dependent autophagy |
topic | Stem Cell Technology: Epigenetics, Genomics, Proteomics, and Metabonomics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916635/ https://www.ncbi.nlm.nih.gov/pubmed/31574189 http://dx.doi.org/10.1002/stem.3091 |
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