Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Osteogenic Differentiation by Modulating AMPK/ULK1‐Dependent Autophagy
Identifieur interne : 000623 ( Main/Exploration ); précédent : 000622; suivant : 000624Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Osteogenic Differentiation by Modulating AMPK/ULK1‐Dependent Autophagy
Auteurs : Zheng Li ; Xuenan Liu ; Yuan Zhu ; Yangge Du ; Xuejiao Liu ; Longwei Lv ; Xiao Zhang ; Yunsong Liu ; Ping Zhang ; Yongsheng ZhouSource :
- Stem Cells (Dayton, Ohio) [ 1066-5099 ] ; 2019.
Abstract
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.
Url:
DOI: 10.1002/stem.3091
PubMed: 31574189
PubMed Central: 6916635
Affiliations:
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id="stem3091-aff-0002"></nlm:aff></affiliation></author><author><name sortKey="Du, Yangge" sort="Du, Yangge" uniqKey="Du Y" first="Yangge" last="Du">Yangge Du</name><affiliation><nlm:aff id="stem3091-aff-0001"></nlm:aff></affiliation><affiliation><nlm:aff id="stem3091-aff-0002"></nlm:aff></affiliation></author><author><name sortKey="Liu, Xuejiao" sort="Liu, Xuejiao" uniqKey="Liu X" first="Xuejiao" last="Liu">Xuejiao Liu</name><affiliation><nlm:aff id="stem3091-aff-0001"></nlm:aff></affiliation><affiliation><nlm:aff id="stem3091-aff-0002"></nlm:aff></affiliation></author><author><name sortKey="Lv, Longwei" sort="Lv, Longwei" uniqKey="Lv L" first="Longwei" last="Lv">Longwei Lv</name><affiliation><nlm:aff id="stem3091-aff-0001"></nlm:aff></affiliation><affiliation><nlm:aff id="stem3091-aff-0002"></nlm:aff></affiliation></author><author><name sortKey="Zhang, Xiao" sort="Zhang, Xiao" uniqKey="Zhang X" first="Xiao" last="Zhang">Xiao Zhang</name><affiliation><nlm:aff 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Ohio)</title><idno type="ISSN">1066-5099</idno><idno type="eISSN">1549-4918</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Abstract</title><p>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. <sc>stem cells</sc><italic>2019;37:1542–1555</italic></p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Du, Yangge" sort="Du, Yangge" uniqKey="Du Y" first="Yangge" last="Du">Yangge Du</name><name sortKey="Li, Zheng" sort="Li, Zheng" uniqKey="Li Z" first="Zheng" last="Li">Zheng Li</name><name sortKey="Liu, Xuejiao" sort="Liu, Xuejiao" uniqKey="Liu X" first="Xuejiao" last="Liu">Xuejiao Liu</name><name sortKey="Liu, Xuenan" sort="Liu, Xuenan" uniqKey="Liu X" first="Xuenan" last="Liu">Xuenan Liu</name><name sortKey="Liu, Yunsong" sort="Liu, Yunsong" uniqKey="Liu Y" first="Yunsong" last="Liu">Yunsong Liu</name><name sortKey="Lv, Longwei" sort="Lv, Longwei" uniqKey="Lv L" first="Longwei" last="Lv">Longwei Lv</name><name sortKey="Zhang, Ping" sort="Zhang, Ping" uniqKey="Zhang P" first="Ping" last="Zhang">Ping Zhang</name><name sortKey="Zhang, Xiao" sort="Zhang, Xiao" uniqKey="Zhang X" first="Xiao" last="Zhang">Xiao Zhang</name><name sortKey="Zhou, Yongsheng" sort="Zhou, Yongsheng" uniqKey="Zhou Y" first="Yongsheng" last="Zhou">Yongsheng Zhou</name><name sortKey="Zhu, Yuan" sort="Zhu, Yuan" uniqKey="Zhu Y" first="Yuan" last="Zhu">Yuan Zhu</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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