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Epigenetic inhibition of Wnt pathway suppresses osteogenic differentiation of BMSCs during osteoporosis

Disrupted Wnt signaling in osteoblastic-lineage cells leads to bone formation defect in osteoporosis. However, the factors repressing Wnt signaling are unclear. In our study, we found that Wnt signaling was suppressed persistently in bone marrow-derived mesenchymal stem cells (BMSCs) during osteopor...

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Autores principales: Jing, Huan, Su, Xiaoxia, Gao, Bo, Shuai, Yi, Chen, Ji, Deng, Zhihong, Liao, Li, Jin, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833865/
https://www.ncbi.nlm.nih.gov/pubmed/29416009
http://dx.doi.org/10.1038/s41419-017-0231-0
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author Jing, Huan
Su, Xiaoxia
Gao, Bo
Shuai, Yi
Chen, Ji
Deng, Zhihong
Liao, Li
Jin, Yan
author_facet Jing, Huan
Su, Xiaoxia
Gao, Bo
Shuai, Yi
Chen, Ji
Deng, Zhihong
Liao, Li
Jin, Yan
author_sort Jing, Huan
collection PubMed
description Disrupted Wnt signaling in osteoblastic-lineage cells leads to bone formation defect in osteoporosis. However, the factors repressing Wnt signaling are unclear. In our study, we found that Wnt signaling was suppressed persistently in bone marrow-derived mesenchymal stem cells (BMSCs) during osteoporosis. Accordingly, histone acetylation levels on Wnt genes (Wnt1, Wnt6, Wnt10a, and Wnt10b) were declined in BMSCs from OVX mice. By screening the family of histone acetyltransferase, we identified that GCN5 expression increased during osteogenic differentiation of BMSCs, whereas decreased after osteoporosis. Further analysis revealed that GCN5 promoted osteogenic differentiation of BMSCs by increasing acetylation on histone 3 lysine 9 loci on the promoters of Wnt genes. Reduced GCN5 expression suppressed Wnt signaling, resulting in osteogenic defect of BMSCs from OVX mice. Moreover, restoring GCN5 levels recovered BMSC osteogenic differentiation, and attenuated bone loss in OVX mice. Taken together, our study demonstrated that disrupted histone acetylation modification in BMSCs lead to bone formation defect during osteoporosis. The findings also introduced a novel therapeutic target for osteoporosis.
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spelling pubmed-58338652018-03-06 Epigenetic inhibition of Wnt pathway suppresses osteogenic differentiation of BMSCs during osteoporosis Jing, Huan Su, Xiaoxia Gao, Bo Shuai, Yi Chen, Ji Deng, Zhihong Liao, Li Jin, Yan Cell Death Dis Article Disrupted Wnt signaling in osteoblastic-lineage cells leads to bone formation defect in osteoporosis. However, the factors repressing Wnt signaling are unclear. In our study, we found that Wnt signaling was suppressed persistently in bone marrow-derived mesenchymal stem cells (BMSCs) during osteoporosis. Accordingly, histone acetylation levels on Wnt genes (Wnt1, Wnt6, Wnt10a, and Wnt10b) were declined in BMSCs from OVX mice. By screening the family of histone acetyltransferase, we identified that GCN5 expression increased during osteogenic differentiation of BMSCs, whereas decreased after osteoporosis. Further analysis revealed that GCN5 promoted osteogenic differentiation of BMSCs by increasing acetylation on histone 3 lysine 9 loci on the promoters of Wnt genes. Reduced GCN5 expression suppressed Wnt signaling, resulting in osteogenic defect of BMSCs from OVX mice. Moreover, restoring GCN5 levels recovered BMSC osteogenic differentiation, and attenuated bone loss in OVX mice. Taken together, our study demonstrated that disrupted histone acetylation modification in BMSCs lead to bone formation defect during osteoporosis. The findings also introduced a novel therapeutic target for osteoporosis. Nature Publishing Group UK 2018-02-07 /pmc/articles/PMC5833865/ /pubmed/29416009 http://dx.doi.org/10.1038/s41419-017-0231-0 Text en © The Author(s) 2018 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/.
spellingShingle Article
Jing, Huan
Su, Xiaoxia
Gao, Bo
Shuai, Yi
Chen, Ji
Deng, Zhihong
Liao, Li
Jin, Yan
Epigenetic inhibition of Wnt pathway suppresses osteogenic differentiation of BMSCs during osteoporosis
title Epigenetic inhibition of Wnt pathway suppresses osteogenic differentiation of BMSCs during osteoporosis
title_full Epigenetic inhibition of Wnt pathway suppresses osteogenic differentiation of BMSCs during osteoporosis
title_fullStr Epigenetic inhibition of Wnt pathway suppresses osteogenic differentiation of BMSCs during osteoporosis
title_full_unstemmed Epigenetic inhibition of Wnt pathway suppresses osteogenic differentiation of BMSCs during osteoporosis
title_short Epigenetic inhibition of Wnt pathway suppresses osteogenic differentiation of BMSCs during osteoporosis
title_sort epigenetic inhibition of wnt pathway suppresses osteogenic differentiation of bmscs during osteoporosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833865/
https://www.ncbi.nlm.nih.gov/pubmed/29416009
http://dx.doi.org/10.1038/s41419-017-0231-0
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