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1,25(OH)(2)D(3) inhibits osteogenic differentiation through activating β-catenin signaling via downregulating bone morphogenetic protein 2
The present study explored whether bone morphogenetic proteins (BMPs) and Wnt/β-catenin signaling pathways were involved in the 1,25(OH)(2)D(3)-induced inhibition of osteogenic differentiation in bone marrow-derived mesenchymal stem cells (BMSCs). To evaluate the osteogenic differentiation of BMSCs,...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646955/ https://www.ncbi.nlm.nih.gov/pubmed/33173996 http://dx.doi.org/10.3892/mmr.2020.11619 |
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author | Han, Xiaofeng Zhu, Naifeng Wang, Yihan Cheng, Guangqi |
author_facet | Han, Xiaofeng Zhu, Naifeng Wang, Yihan Cheng, Guangqi |
author_sort | Han, Xiaofeng |
collection | PubMed |
description | The present study explored whether bone morphogenetic proteins (BMPs) and Wnt/β-catenin signaling pathways were involved in the 1,25(OH)(2)D(3)-induced inhibition of osteogenic differentiation in bone marrow-derived mesenchymal stem cells (BMSCs). To evaluate the osteogenic differentiation of BMSCs, the expression levels of ossification markers, including BMP2, Runt-related transcription factor 2 (Runx2), Msh homeobox 2 (Msx2), osteopontin (OPN) and osteocalcin (OCN), and the activity of alkaline phosphatase (ALP), as well as the calcified area observed by Alizarin red-S staining, were investigated. Chromatin immunoprecipitation (ChIP) assay was used to detect the effect of 1,25(OH)(2)D(3) on the DNA methylation and histone modification of BMP2, while an immunoprecipitation (IP) assay was performed to assess the crosstalk between Smad1 and disheveled-1 (Dvl-1) proteins. It was observed that 1,25(OH)(2)D(3) significantly decreased the expression levels of BMP2, Runx2, Msx2, OPN and OCN, and reduced ALP activity and the calcified area in BMSCs, whereas these effects were rescued by BMP2 overexpression. ChIP assay revealed that BMSCs treated with 1,25(OH)(2)D(3) exhibited a significant increase in H3K9me2 level and a decrease in the acetylation of histone H3 at the same BMP2 promoter region. In addition, 1,25(OH)(2)D(3) treatment promoted the nuclear accumulation of β-catenin by downregulating BMP2. Furthermore, the β-catenin signaling inhibitor XAV-939 weakened the inhibitory effect of 1,25(OH)(2)D(3) on osteogenic differentiation. Additionally, knockdown of β-catenin rescued the attenuation in Dvl-1 and Smad1 interaction caused by 1,25(OH)(2)D(3). Overexpression of Smad1 also reversed the inhibitory effect of 1,25(OH)(2)D(3) on osteogenic differentiation. Taken together, the current study demonstrated that 1,25(OH)(2)D(3) inhibited the differentiation of BMSCs into osteoblast-like cells by inactivating BMP2 and activating Wnt/β-catenin signaling. |
format | Online Article Text |
id | pubmed-7646955 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-76469552020-11-13 1,25(OH)(2)D(3) inhibits osteogenic differentiation through activating β-catenin signaling via downregulating bone morphogenetic protein 2 Han, Xiaofeng Zhu, Naifeng Wang, Yihan Cheng, Guangqi Mol Med Rep Articles The present study explored whether bone morphogenetic proteins (BMPs) and Wnt/β-catenin signaling pathways were involved in the 1,25(OH)(2)D(3)-induced inhibition of osteogenic differentiation in bone marrow-derived mesenchymal stem cells (BMSCs). To evaluate the osteogenic differentiation of BMSCs, the expression levels of ossification markers, including BMP2, Runt-related transcription factor 2 (Runx2), Msh homeobox 2 (Msx2), osteopontin (OPN) and osteocalcin (OCN), and the activity of alkaline phosphatase (ALP), as well as the calcified area observed by Alizarin red-S staining, were investigated. Chromatin immunoprecipitation (ChIP) assay was used to detect the effect of 1,25(OH)(2)D(3) on the DNA methylation and histone modification of BMP2, while an immunoprecipitation (IP) assay was performed to assess the crosstalk between Smad1 and disheveled-1 (Dvl-1) proteins. It was observed that 1,25(OH)(2)D(3) significantly decreased the expression levels of BMP2, Runx2, Msx2, OPN and OCN, and reduced ALP activity and the calcified area in BMSCs, whereas these effects were rescued by BMP2 overexpression. ChIP assay revealed that BMSCs treated with 1,25(OH)(2)D(3) exhibited a significant increase in H3K9me2 level and a decrease in the acetylation of histone H3 at the same BMP2 promoter region. In addition, 1,25(OH)(2)D(3) treatment promoted the nuclear accumulation of β-catenin by downregulating BMP2. Furthermore, the β-catenin signaling inhibitor XAV-939 weakened the inhibitory effect of 1,25(OH)(2)D(3) on osteogenic differentiation. Additionally, knockdown of β-catenin rescued the attenuation in Dvl-1 and Smad1 interaction caused by 1,25(OH)(2)D(3). Overexpression of Smad1 also reversed the inhibitory effect of 1,25(OH)(2)D(3) on osteogenic differentiation. Taken together, the current study demonstrated that 1,25(OH)(2)D(3) inhibited the differentiation of BMSCs into osteoblast-like cells by inactivating BMP2 and activating Wnt/β-catenin signaling. D.A. Spandidos 2020-12 2020-10-20 /pmc/articles/PMC7646955/ /pubmed/33173996 http://dx.doi.org/10.3892/mmr.2020.11619 Text en Copyright: © Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Han, Xiaofeng Zhu, Naifeng Wang, Yihan Cheng, Guangqi 1,25(OH)(2)D(3) inhibits osteogenic differentiation through activating β-catenin signaling via downregulating bone morphogenetic protein 2 |
title | 1,25(OH)(2)D(3) inhibits osteogenic differentiation through activating β-catenin signaling via downregulating bone morphogenetic protein 2 |
title_full | 1,25(OH)(2)D(3) inhibits osteogenic differentiation through activating β-catenin signaling via downregulating bone morphogenetic protein 2 |
title_fullStr | 1,25(OH)(2)D(3) inhibits osteogenic differentiation through activating β-catenin signaling via downregulating bone morphogenetic protein 2 |
title_full_unstemmed | 1,25(OH)(2)D(3) inhibits osteogenic differentiation through activating β-catenin signaling via downregulating bone morphogenetic protein 2 |
title_short | 1,25(OH)(2)D(3) inhibits osteogenic differentiation through activating β-catenin signaling via downregulating bone morphogenetic protein 2 |
title_sort | 1,25(oh)(2)d(3) inhibits osteogenic differentiation through activating β-catenin signaling via downregulating bone morphogenetic protein 2 |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646955/ https://www.ncbi.nlm.nih.gov/pubmed/33173996 http://dx.doi.org/10.3892/mmr.2020.11619 |
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