Chromatin remodeling and nucleoskeleton synergistically control osteogenic differentiation in different matrix stiffnesses

作者全名："Xu, Xinxin; Zhang, He; Li, Yuzhou; Liu, Fengyi; Jing, Zheng; Ren, Mingxing; Chen, Tao; Fu, Yiru; Wu, Yanqiu; Ji, Ping; Yang, Sheng"

作者地址："[Xu, Xinxin; Zhang, He; Li, Yuzhou; Liu, Fengyi; Jing, Zheng; Ren, Mingxing; Chen, Tao; Fu, Yiru; Wu, Yanqiu; Ji, Ping; Yang, Sheng] Chongqing Med Univ, Coll Stomatol, Chongqing, Peoples R China; [Xu, Xinxin; Zhang, He; Li, Yuzhou; Liu, Fengyi; Jing, Zheng; Ren, Mingxing; Chen, Tao; Fu, Yiru; Wu, Yanqiu; Ji, Ping; Yang, Sheng] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China; [Xu, Xinxin; Zhang, He; Li, Yuzhou; Liu, Fengyi; Jing, Zheng; Ren, Mingxing; Chen, Tao; Fu, Yiru; Wu, Yanqiu; Ji, Ping; Yang, Sheng] Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China; [Yang, Sheng] Chongqing Med Univ, Stomatol Hosp, Coll Stomatol, Chongqing Key Lab Oral Dis & Biomed Sci, 426 Songshi North Rd, Chongqing 401147, Peoples R China"

通信作者："Zhang, H; Ji, P; Yang, S (通讯作者)，Chongqing Med Univ, Coll Stomatol, Chongqing, Peoples R China.; Zhang, H; Ji, P; Yang, S (通讯作者)，Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China.; Yang, S (通讯作者)，Chongqing Med Univ, Stomatol Hosp, Coll Stomatol, Chongqing Key Lab Oral Dis & Biomed Sci, 426 Songshi North Rd, Chongqing 401147, Peoples R China."

来源：MATERIALS TODAY BIO

ESI学科分类：　

WOS号：WOS:001004335800001

JCR分区：Q1

影响因子：8.7

年份：2023

卷号：20

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Matrix stiffness; Chromatin remodeling; Lamin A; C; Mechanotransduction; Osteogenic differentiation

摘要："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 beta-catenin target genes (Axin2, c-Myc). Histone deacetylase inhibitor (TSA) was used to decondense chromatin. However, there was no significant in-crease in the expression of beta-catenin target genes and the osteogenic protein Runx2. Further studies revealed that beta-catenin was restricted to the cytoplasm due to the downregulation of lamin A/C in the soft matrix. Over -expression of lamin A/C and concomitant treatment of cells with TSA successfully activated beta-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."

基金机构："National Natural Science Foundation of China [82171010, 82220108019, 82170936, 82001103, 82270962]; Natural Science Foundation of Chongqing [cstc2021jcyj-jqX0028, CSTB2022NSCQ-MSX0098]; Chongqing Sci- ence and Health Joint Project [2020GDRC015]; CQMU Program for Youth Innovation in Future Medicine [W0079]; Scienti fi c and Technological Research Program of Chongqing Municipal Education Commission [KJQN202200422]; Chongqing Scienti fi c Research and Innovation Project for Postgraduates [CYB21188, CYB22216]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (Grant No. 82171010, 82220108019, 82170936, 82001103, 82270962) , the Natural Science Foundation of Chongqing (Grant No. cstc2021jcyj-jqX0028, CSTB2022NSCQ-MSX0098) , the Chongqing Sci- ence and Health Joint Project (Grant No. 2020GDRC015) , the CQMU Program for Youth Innovation in Future Medicine (Grant No. W0079) , the Scienti fi c and Technological Research Program of Chongqing Municipal Education Commission (Grant No. KJQN202200422) , the Chongqing Scienti fi c Research and Innovation Project for Postgraduates (Grant NO. CYB21188, CYB22216) ."