https://scholars.lib.ntu.edu.tw/handle/123456789/627463
Title: | Wnt antagonism without TGFβ induces rapid MSC chondrogenesis via increasing AJ interactions and restricting lineage commitment | Authors: | Hsieh, Chen-Chan Yen, B Linju Chang, Chia-Chi Hsu, Pei-Ju Lee, Yu-Wei MEN-LUH YEN Yet, Shaw-Fang Chen, Linyi |
Keywords: | Bioengineering; Biological sciences; Molecular medicine; Tissue engineering | Issue Date: | 20-Jan-2023 | Publisher: | CELL PRESS | Journal Volume: | 26 | Journal Issue: | 1 | Source: | iScience | Abstract: | 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 TGFβ, 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/β-catenin antagonism alone without TGFβ. Compared to TGFβ, Wnt/β-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 β-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/β-catenin and TGFβ signaling along with upregulation of α-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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/627463 | ISSN: | 25890042 | DOI: | 10.1016/j.isci.2022.105713 |
Appears in Collections: | 醫學系 |
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