Chromatin remodeling and nucleoskeleton synergistically control osteogenic differentiation in different matrix stiffnesses
Matrix stiffness plays an important role in determining cell differentiation. The expression of cell differentiation-associated genes can be regulated by chromatin remodeling-mediated DNA accessibility. However, the effect of matrix stiffness on DNA accessibility and its significance for cell differ...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006423001217 |
| _version_ | 1827917753390989312 |
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| author | Xinxin Xu He Zhang Yuzhou Li Fengyi Liu Zheng Jing Mingxing Ren Tao Chen Yiru Fu Yanqiu Wu Ping Ji Sheng Yang |
| author_facet | Xinxin Xu He Zhang Yuzhou Li Fengyi Liu Zheng Jing Mingxing Ren Tao Chen Yiru Fu Yanqiu Wu Ping Ji Sheng Yang |
| author_sort | Xinxin Xu |
| collection | DOAJ |
| description | Matrix stiffness plays an important role in determining cell differentiation. The expression of cell differentiation-associated genes can be regulated by chromatin remodeling-mediated DNA accessibility. However, the effect of matrix stiffness on DNA accessibility and its significance for cell differentiation have not been investigated. In this study, gelatin methacryloyl (GelMA) hydrogels with different degrees of substitution were used to simulate soft, medium, and stiff matrices, and it was found that a stiff matrix promoted osteogenic differentiation of MC3T3-E1 cells by activating the Wnt pathway. In the soft matrix, the acetylation level of histones in cells was decreased, and chromatin condensed into a closed conformation, affecting the activation of β-catenin target genes (Axin2, c-Myc). Histone deacetylase inhibitor (TSA) was used to decondense chromatin. However, there was no significant increase in the expression of β-catenin target genes and the osteogenic protein Runx2. Further studies revealed that β-catenin was restricted to the cytoplasm due to the downregulation of lamin A/C in the soft matrix. Overexpression of lamin A/C and concomitant treatment of cells with TSA successfully activated β-catenin/Wnt signaling in cells in the soft matrix. The results of this innovative study revealed that matrix stiffness regulates cell osteogenic differentiation through multiple pathways, which involve complex interactions between transcription factors, epigenetic modifications of histones, and the nucleoskeleton. This trio is critical for the future design of bionic extracellular matrix biomaterials. |
| first_indexed | 2024-03-13T03:32:56Z |
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| id | doaj.art-f34d74dcd1994d5995f22bdb97b3b38e |
| institution | Directory Open Access Journal |
| issn | 2590-0064 |
| language | English |
| last_indexed | 2024-03-13T03:32:56Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj.art-f34d74dcd1994d5995f22bdb97b3b38e2023-06-24T05:18:41ZengElsevierMaterials Today Bio2590-00642023-06-0120100661Chromatin remodeling and nucleoskeleton synergistically control osteogenic differentiation in different matrix stiffnessesXinxin Xu0He Zhang1Yuzhou Li2Fengyi Liu3Zheng Jing4Mingxing Ren5Tao Chen6Yiru Fu7Yanqiu Wu8Ping Ji9Sheng Yang10College of Stomatology, Chongqing Medical University, PR China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, PR ChinaCollege of Stomatology, Chongqing Medical University, PR China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, PR China; Corresponding author. College of Stomatology, Chongqing Medical University, PR China.College of Stomatology, Chongqing Medical University, PR China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, PR ChinaCollege of Stomatology, Chongqing Medical University, PR China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, PR ChinaCollege of Stomatology, Chongqing Medical University, PR China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, PR ChinaCollege of Stomatology, Chongqing Medical University, PR China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, PR ChinaCollege of Stomatology, Chongqing Medical University, PR China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, PR ChinaCollege of Stomatology, Chongqing Medical University, PR China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, PR ChinaCollege of Stomatology, Chongqing Medical University, PR China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, PR ChinaCollege of Stomatology, Chongqing Medical University, PR China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, PR China; Corresponding author.Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, PR China.College of Stomatology, Chongqing Medical University, PR China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, PR China; Corresponding author. Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Stomatological Hospital of Chongqing Medical University, College of Stomatology, Chongqing Medical University, China, 426 Songshi North Road, Yubei District, Chongqing, 401147, PR China.Matrix stiffness plays an important role in determining cell differentiation. The expression of cell differentiation-associated genes can be regulated by chromatin remodeling-mediated DNA accessibility. However, the effect of matrix stiffness on DNA accessibility and its significance for cell differentiation have not been investigated. In this study, gelatin methacryloyl (GelMA) hydrogels with different degrees of substitution were used to simulate soft, medium, and stiff matrices, and it was found that a stiff matrix promoted osteogenic differentiation of MC3T3-E1 cells by activating the Wnt pathway. In the soft matrix, the acetylation level of histones in cells was decreased, and chromatin condensed into a closed conformation, affecting the activation of β-catenin target genes (Axin2, c-Myc). Histone deacetylase inhibitor (TSA) was used to decondense chromatin. However, there was no significant increase in the expression of β-catenin target genes and the osteogenic protein Runx2. Further studies revealed that β-catenin was restricted to the cytoplasm due to the downregulation of lamin A/C in the soft matrix. Overexpression of lamin A/C and concomitant treatment of cells with TSA successfully activated β-catenin/Wnt signaling in cells in the soft matrix. The results of this innovative study revealed that matrix stiffness regulates cell osteogenic differentiation through multiple pathways, which involve complex interactions between transcription factors, epigenetic modifications of histones, and the nucleoskeleton. This trio is critical for the future design of bionic extracellular matrix biomaterials.http://www.sciencedirect.com/science/article/pii/S2590006423001217Matrix stiffnessChromatin remodelingLamin A/CMechanotransductionOsteogenic differentiation |
| spellingShingle | Xinxin Xu He Zhang Yuzhou Li Fengyi Liu Zheng Jing Mingxing Ren Tao Chen Yiru Fu Yanqiu Wu Ping Ji Sheng Yang Chromatin remodeling and nucleoskeleton synergistically control osteogenic differentiation in different matrix stiffnesses Materials Today Bio Matrix stiffness Chromatin remodeling Lamin A/C Mechanotransduction Osteogenic differentiation |
| title | Chromatin remodeling and nucleoskeleton synergistically control osteogenic differentiation in different matrix stiffnesses |
| title_full | Chromatin remodeling and nucleoskeleton synergistically control osteogenic differentiation in different matrix stiffnesses |
| title_fullStr | Chromatin remodeling and nucleoskeleton synergistically control osteogenic differentiation in different matrix stiffnesses |
| title_full_unstemmed | Chromatin remodeling and nucleoskeleton synergistically control osteogenic differentiation in different matrix stiffnesses |
| title_short | Chromatin remodeling and nucleoskeleton synergistically control osteogenic differentiation in different matrix stiffnesses |
| title_sort | chromatin remodeling and nucleoskeleton synergistically control osteogenic differentiation in different matrix stiffnesses |
| topic | Matrix stiffness Chromatin remodeling Lamin A/C Mechanotransduction Osteogenic differentiation |
| url | http://www.sciencedirect.com/science/article/pii/S2590006423001217 |
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