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A critical bioenergetic switch is regulated by IGF2 during murine cartilage development
Long bone growth requires the precise control of chondrocyte maturation from proliferation to hypertrophy during endochondral ossification, but the bioenergetic program that ensures normal cartilage development is still largely elusive. We show that chondrocytes have unique glucose metabolism signat...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9652369/ https://www.ncbi.nlm.nih.gov/pubmed/36369360 http://dx.doi.org/10.1038/s42003-022-04156-4 |
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author | Hollander, Judith M. Li, Lingyun Rawal, Miraj Wang, Si Kun Shu, Yue Zhang, Ming Nielsen, Heber C. Rosen, Clifford J. Zeng, Li |
author_facet | Hollander, Judith M. Li, Lingyun Rawal, Miraj Wang, Si Kun Shu, Yue Zhang, Ming Nielsen, Heber C. Rosen, Clifford J. Zeng, Li |
author_sort | Hollander, Judith M. |
collection | PubMed |
description | Long bone growth requires the precise control of chondrocyte maturation from proliferation to hypertrophy during endochondral ossification, but the bioenergetic program that ensures normal cartilage development is still largely elusive. We show that chondrocytes have unique glucose metabolism signatures in these stages, and they undergo bioenergetic reprogramming from glycolysis to oxidative phosphorylation during maturation, accompanied by an upregulation of the pentose phosphate pathway. Inhibition of either oxidative phosphorylation or the pentose phosphate pathway in murine chondrocytes and bone organ cultures impaired hypertrophic differentiation, suggesting that the appropriate balance of these pathways is required for cartilage development. Insulin-like growth factor 2 (IGF2) deficiency resulted in a profound increase in oxidative phosphorylation in hypertrophic chondrocytes, suggesting that IGF2 is required to prevent overactive glucose metabolism and maintain a proper balance of metabolic pathways. Our results thus provide critical evidence of preference for a bioenergetic pathway in different stages of chondrocytes and highlight its importance as a fundamental mechanism in skeletal development. |
format | Online Article Text |
id | pubmed-9652369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-96523692022-11-15 A critical bioenergetic switch is regulated by IGF2 during murine cartilage development Hollander, Judith M. Li, Lingyun Rawal, Miraj Wang, Si Kun Shu, Yue Zhang, Ming Nielsen, Heber C. Rosen, Clifford J. Zeng, Li Commun Biol Article Long bone growth requires the precise control of chondrocyte maturation from proliferation to hypertrophy during endochondral ossification, but the bioenergetic program that ensures normal cartilage development is still largely elusive. We show that chondrocytes have unique glucose metabolism signatures in these stages, and they undergo bioenergetic reprogramming from glycolysis to oxidative phosphorylation during maturation, accompanied by an upregulation of the pentose phosphate pathway. Inhibition of either oxidative phosphorylation or the pentose phosphate pathway in murine chondrocytes and bone organ cultures impaired hypertrophic differentiation, suggesting that the appropriate balance of these pathways is required for cartilage development. Insulin-like growth factor 2 (IGF2) deficiency resulted in a profound increase in oxidative phosphorylation in hypertrophic chondrocytes, suggesting that IGF2 is required to prevent overactive glucose metabolism and maintain a proper balance of metabolic pathways. Our results thus provide critical evidence of preference for a bioenergetic pathway in different stages of chondrocytes and highlight its importance as a fundamental mechanism in skeletal development. Nature Publishing Group UK 2022-11-11 /pmc/articles/PMC9652369/ /pubmed/36369360 http://dx.doi.org/10.1038/s42003-022-04156-4 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 Hollander, Judith M. Li, Lingyun Rawal, Miraj Wang, Si Kun Shu, Yue Zhang, Ming Nielsen, Heber C. Rosen, Clifford J. Zeng, Li A critical bioenergetic switch is regulated by IGF2 during murine cartilage development |
title | A critical bioenergetic switch is regulated by IGF2 during murine cartilage development |
title_full | A critical bioenergetic switch is regulated by IGF2 during murine cartilage development |
title_fullStr | A critical bioenergetic switch is regulated by IGF2 during murine cartilage development |
title_full_unstemmed | A critical bioenergetic switch is regulated by IGF2 during murine cartilage development |
title_short | A critical bioenergetic switch is regulated by IGF2 during murine cartilage development |
title_sort | critical bioenergetic switch is regulated by igf2 during murine cartilage development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9652369/ https://www.ncbi.nlm.nih.gov/pubmed/36369360 http://dx.doi.org/10.1038/s42003-022-04156-4 |
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