Hsieh, Chen-ChanChen-ChanHsiehYen, B LinjuB LinjuYenChang, Chia-ChiChia-ChiChangHsu, Pei-JuPei-JuHsuLee, Yu-WeiYu-WeiLeeMEN-LUH YENYet, Shaw-FangShaw-FangYetChen, LinyiLinyiChen2023-01-192023-01-192023-01-2025890042https://scholars.lib.ntu.edu.tw/handle/123456789/627463Human 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.enBioengineering; Biological sciences; Molecular medicine; Tissue engineeringjournal article10.1016/j.isci.2022.105713365828232-s2.0-85144426378WOS:000901510100003https://api.elsevier.com/content/abstract/scopus_id/85144426378