Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Zheng, Liu, Xuenan, Zhu, Yuan, Du, Yangge, Liu, Xuejiao, Lv, Longwei, Zhang, Xiao, Liu, Yunsong, Zhang, Ping, Zhou, Yongsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2019
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
_version_ 1783480273307959296
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
work_keys_str_mv AT lizheng mitochondrialphosphoenolpyruvatecarboxykinaseregulatesosteogenicdifferentiationbymodulatingampkulk1dependentautophagy
AT liuxuenan mitochondrialphosphoenolpyruvatecarboxykinaseregulatesosteogenicdifferentiationbymodulatingampkulk1dependentautophagy
AT zhuyuan mitochondrialphosphoenolpyruvatecarboxykinaseregulatesosteogenicdifferentiationbymodulatingampkulk1dependentautophagy
AT duyangge mitochondrialphosphoenolpyruvatecarboxykinaseregulatesosteogenicdifferentiationbymodulatingampkulk1dependentautophagy
AT liuxuejiao mitochondrialphosphoenolpyruvatecarboxykinaseregulatesosteogenicdifferentiationbymodulatingampkulk1dependentautophagy
AT lvlongwei mitochondrialphosphoenolpyruvatecarboxykinaseregulatesosteogenicdifferentiationbymodulatingampkulk1dependentautophagy
AT zhangxiao mitochondrialphosphoenolpyruvatecarboxykinaseregulatesosteogenicdifferentiationbymodulatingampkulk1dependentautophagy
AT liuyunsong mitochondrialphosphoenolpyruvatecarboxykinaseregulatesosteogenicdifferentiationbymodulatingampkulk1dependentautophagy
AT zhangping mitochondrialphosphoenolpyruvatecarboxykinaseregulatesosteogenicdifferentiationbymodulatingampkulk1dependentautophagy
AT zhouyongsheng mitochondrialphosphoenolpyruvatecarboxykinaseregulatesosteogenicdifferentiationbymodulatingampkulk1dependentautophagy