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A Lox/CHOP‐10 crosstalk governs osteogenic and adipogenic cell fate by MSCs

Accelerated marrow adipogenesis has been associated with ageing and osteoporosis and is thought to be because of an imbalance between adipogenic and osteogenic differentiation of mesenchymal stem cell (MSCs). We have previously found that lysyl oxidase (Lox) inhibition disrupts BMP4‐induced adipocyt...

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Autores principales: Jiang, Wen‐yan, Xing, Chun, Wang, Hong‐wei, Wang, Wei, Chen, Su‐zhen, Ning, Liu‐fang, Xu, Xu, Tang, Qi‐qun, Huang, Hai‐yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156357/
https://www.ncbi.nlm.nih.gov/pubmed/30044535
http://dx.doi.org/10.1111/jcmm.13798
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author Jiang, Wen‐yan
Xing, Chun
Wang, Hong‐wei
Wang, Wei
Chen, Su‐zhen
Ning, Liu‐fang
Xu, Xu
Tang, Qi‐qun
Huang, Hai‐yan
author_facet Jiang, Wen‐yan
Xing, Chun
Wang, Hong‐wei
Wang, Wei
Chen, Su‐zhen
Ning, Liu‐fang
Xu, Xu
Tang, Qi‐qun
Huang, Hai‐yan
author_sort Jiang, Wen‐yan
collection PubMed
description Accelerated marrow adipogenesis has been associated with ageing and osteoporosis and is thought to be because of an imbalance between adipogenic and osteogenic differentiation of mesenchymal stem cell (MSCs). We have previously found that lysyl oxidase (Lox) inhibition disrupts BMP4‐induced adipocytic lineage commitment and differentiation of MSCs. In this study, we found that lox inhibition dramatically up‐regulates BMP4‐induced expression of CCAAT/enhancer binding protein (C/EBP) homologous protein 10 (CHOP‐10), which then promotes BMP4‐induced osteogenesis of MSCs both in vitro and in vivo. Specifically, Lox inhibition or CHOP‐10 up‐regulation activated Wnt/β‐catenin signalling to enhance BMP4‐induced osteogenesis, with pro‐adipogenic p38 MAPK and Smad signalling suppressed. Together, we demonstrate that Lox/CHOP‐10 crosstalk regulates BMP4‐induced osteogenic and adipogenic fate determination of MSCs, presenting a promising therapeutic target for osteoporosis and other bone diseases.
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spelling pubmed-61563572018-10-01 A Lox/CHOP‐10 crosstalk governs osteogenic and adipogenic cell fate by MSCs Jiang, Wen‐yan Xing, Chun Wang, Hong‐wei Wang, Wei Chen, Su‐zhen Ning, Liu‐fang Xu, Xu Tang, Qi‐qun Huang, Hai‐yan J Cell Mol Med Original Articles Accelerated marrow adipogenesis has been associated with ageing and osteoporosis and is thought to be because of an imbalance between adipogenic and osteogenic differentiation of mesenchymal stem cell (MSCs). We have previously found that lysyl oxidase (Lox) inhibition disrupts BMP4‐induced adipocytic lineage commitment and differentiation of MSCs. In this study, we found that lox inhibition dramatically up‐regulates BMP4‐induced expression of CCAAT/enhancer binding protein (C/EBP) homologous protein 10 (CHOP‐10), which then promotes BMP4‐induced osteogenesis of MSCs both in vitro and in vivo. Specifically, Lox inhibition or CHOP‐10 up‐regulation activated Wnt/β‐catenin signalling to enhance BMP4‐induced osteogenesis, with pro‐adipogenic p38 MAPK and Smad signalling suppressed. Together, we demonstrate that Lox/CHOP‐10 crosstalk regulates BMP4‐induced osteogenic and adipogenic fate determination of MSCs, presenting a promising therapeutic target for osteoporosis and other bone diseases. John Wiley and Sons Inc. 2018-07-25 2018-10 /pmc/articles/PMC6156357/ /pubmed/30044535 http://dx.doi.org/10.1111/jcmm.13798 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Jiang, Wen‐yan
Xing, Chun
Wang, Hong‐wei
Wang, Wei
Chen, Su‐zhen
Ning, Liu‐fang
Xu, Xu
Tang, Qi‐qun
Huang, Hai‐yan
A Lox/CHOP‐10 crosstalk governs osteogenic and adipogenic cell fate by MSCs
title A Lox/CHOP‐10 crosstalk governs osteogenic and adipogenic cell fate by MSCs
title_full A Lox/CHOP‐10 crosstalk governs osteogenic and adipogenic cell fate by MSCs
title_fullStr A Lox/CHOP‐10 crosstalk governs osteogenic and adipogenic cell fate by MSCs
title_full_unstemmed A Lox/CHOP‐10 crosstalk governs osteogenic and adipogenic cell fate by MSCs
title_short A Lox/CHOP‐10 crosstalk governs osteogenic and adipogenic cell fate by MSCs
title_sort lox/chop‐10 crosstalk governs osteogenic and adipogenic cell fate by mscs
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156357/
https://www.ncbi.nlm.nih.gov/pubmed/30044535
http://dx.doi.org/10.1111/jcmm.13798
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