國家衛生研究院 NHRI:Item 3990099045/14811
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    题名: Wnt antagonism without TGF beta induces rapid MSC chondrogenesis via increasing AJ interactions and restricting lineage commitment
    其它题名: Wnt antagonism without TGF β induces rapid MSC chondrogenesis via increasing AJ interactions and restricting lineage commitment
    作者: Hsieh, CC;Yen, BL;Chang, CC;Hsu, PJ;Lee, YW;Yen, ML;Yet, SF;Chen, LY
    贡献者: Institute of Cellular and Systems Medicine
    摘要: Human mesenchymal stem cells (MSCs) remain one of the best cell sources for cartilage, a tissue without regenerative capacity. However, MSC chondrogenesis is commonly induced through TGF beta, a pleomorphic growth factor without specificity for this lineage. Using tissue- and induced pluripotent stem cell-derived MSCs, we demonstrate an efficient and precise approach to induce chondrogenesis through Wnt/beta-catenin antagonism alone without TGF beta. Compared to TGF beta, Wnt/beta-catenin antagonism more rapidly induced MSC chondrogenesis without eliciting off-target lineage specification toward smooth muscle or hypertrophy; this was mediated through increasing N-cadherin levels and beta-catenin interactions-key components of the adherens junctions (AJ)-and increasing cytoskeleton-mediated condensation. Validation with transcriptomic analysis of human chondrocytes compared to MSCs and osteoblasts showed significant downregulation of Wnt/beta-catenin and TGF beta signaling along with upregulation of alpha-catenin as an upstream regulator Our findings underscore the importance of understanding developmental pathways and structural modifications in achieving efficient MSC chondrogenesis for translational application.
    日期: 2023-01-20
    關聯: iScience. 2023 Jan 20;26(1):Article number 105713.
    Link to: http://dx.doi.org/10.1016/j.isci.2022.105713
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2589-0042&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000901510100003
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85144426378
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