Downregulating Promotes the Differentiation of Induced Pluripotent Stem Cells into Mesenchymal Stem Cells through the PI3K/Akt/GSK-3β/Wnt Signaling Pathway.

Understanding the mechanism of the differentiation of induced pluripotent stem cells (iPSCs) into mesenchymal stem cells (MSCs) and promoting the production efficiency of iPSC-derived MSCs (iPSC-MSCs) are critical to periodontal tissue engineering. However, the gene networks that control this differentiation process from iPSCs into MSCs are poorly understood. We demonstrated that knockdown showed a positive effect on the triploblastic and MSC differentiation from iPSCs. Activation of the PI3K/Akt signaling pathway by knockdown activated the Wnt/β-catenin signaling pathway by inhibiting GSK-3β and reducing β-catenin degradation. Inhibitor of the PI3K/Akt signaling pathway normalized the enhanced efficiency of differentiation into MSCs of -KD iPSCs and Wnt activator-treated control iPSCs. -OE iPSCs displayed an opposite phenotype. In conclusion, downregulating promotes the differentiation of iPSCs into MSCs by activating the PI3K/Akt/GSK-3β/Wnt signaling pathway. Our results reveal a crucial function and mechanism for in regulating MSC differentiation from iPSCs, which will provide new ideas for periodontal tissue engineering and periodontal regenerative treatment by using iPSC-MSCs.