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Metformin can mitigate skeletal dysplasia caused by Pck2 deficiency

As an important enzyme for gluconeogenesis, mitochondrial phosphoenolpyruvate carboxykinase (PCK2) has further complex functions beyond regulation of glucose metabolism. Here, we report that conditional knockout of Pck2 in osteoblasts results in a pathological phenotype manifested as craniofacial ma...

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Autores principales: Li, Zheng, Yue, Muxin, Heng, Boon Chin, Liu, Yunsong, Zhang, Ping, Zhou, Yongsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9663691/
https://www.ncbi.nlm.nih.gov/pubmed/36376276
http://dx.doi.org/10.1038/s41368-022-00204-1
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author Li, Zheng
Yue, Muxin
Heng, Boon Chin
Liu, Yunsong
Zhang, Ping
Zhou, Yongsheng
author_facet Li, Zheng
Yue, Muxin
Heng, Boon Chin
Liu, Yunsong
Zhang, Ping
Zhou, Yongsheng
author_sort Li, Zheng
collection PubMed
description As an important enzyme for gluconeogenesis, mitochondrial phosphoenolpyruvate carboxykinase (PCK2) has further complex functions beyond regulation of glucose metabolism. Here, we report that conditional knockout of Pck2 in osteoblasts results in a pathological phenotype manifested as craniofacial malformation, long bone loss, and marrow adipocyte accumulation. Ablation of Pck2 alters the metabolic pathways of developing bone, particularly fatty acid metabolism. However, metformin treatment can mitigate skeletal dysplasia of embryonic and postnatal heterozygous knockout mice, at least partly via the AMPK signaling pathway. Collectively, these data illustrate that PCK2 is pivotal for bone development and metabolic homeostasis, and suggest that regulation of metformin-mediated signaling could provide a novel and practical strategy for treating metabolic skeletal dysfunction.
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spelling pubmed-96636912022-11-15 Metformin can mitigate skeletal dysplasia caused by Pck2 deficiency Li, Zheng Yue, Muxin Heng, Boon Chin Liu, Yunsong Zhang, Ping Zhou, Yongsheng Int J Oral Sci Article As an important enzyme for gluconeogenesis, mitochondrial phosphoenolpyruvate carboxykinase (PCK2) has further complex functions beyond regulation of glucose metabolism. Here, we report that conditional knockout of Pck2 in osteoblasts results in a pathological phenotype manifested as craniofacial malformation, long bone loss, and marrow adipocyte accumulation. Ablation of Pck2 alters the metabolic pathways of developing bone, particularly fatty acid metabolism. However, metformin treatment can mitigate skeletal dysplasia of embryonic and postnatal heterozygous knockout mice, at least partly via the AMPK signaling pathway. Collectively, these data illustrate that PCK2 is pivotal for bone development and metabolic homeostasis, and suggest that regulation of metformin-mediated signaling could provide a novel and practical strategy for treating metabolic skeletal dysfunction. Nature Publishing Group UK 2022-11-15 /pmc/articles/PMC9663691/ /pubmed/36376276 http://dx.doi.org/10.1038/s41368-022-00204-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Li, Zheng
Yue, Muxin
Heng, Boon Chin
Liu, Yunsong
Zhang, Ping
Zhou, Yongsheng
Metformin can mitigate skeletal dysplasia caused by Pck2 deficiency
title Metformin can mitigate skeletal dysplasia caused by Pck2 deficiency
title_full Metformin can mitigate skeletal dysplasia caused by Pck2 deficiency
title_fullStr Metformin can mitigate skeletal dysplasia caused by Pck2 deficiency
title_full_unstemmed Metformin can mitigate skeletal dysplasia caused by Pck2 deficiency
title_short Metformin can mitigate skeletal dysplasia caused by Pck2 deficiency
title_sort metformin can mitigate skeletal dysplasia caused by pck2 deficiency
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9663691/
https://www.ncbi.nlm.nih.gov/pubmed/36376276
http://dx.doi.org/10.1038/s41368-022-00204-1
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