Osteoinductive function of fucoidan on periodontal ligament stem cells: Role of PI3K/Akt and Wnt/beta-catenin signaling pathways

Background/Objectives: Fucoidan has been focused as a multifunctional therapeutic uses including bone health supplements. However, the critical molecular mechanisms of fucoidan for bone therapeutic agents have not been fully understood. We investigated the osteoinductive effect of fucoidan on periodontal ligament stem cells (PDLSCs) and how this polymer encouraged PDLSC osteogenesis. Materials and Methods: Osteogenic induction of PDLSCs was processed by culturing cells with fucoidan treatment. Osteogenic differentiation of PDLSCs was verified by alkaline phosphatase (ALP) activity, matrix mineralization assay, intracellular calcium levels, and mRNA expression and protein levels of osteogenic markers. Results: Fucoidan treatment showed higher osteogenic activity in the PDLSCs than the control groups. PDLSCs with fucoidan also presented increased levels of the phosphatidylinositol-3-kinase (PI3K) isoforms, p110 alpha and p110 gamma compared to control cells. The phosphorylation of Akt, a PI3K downstream effector, was significantly increased at 90 min of fucoidan induction. Expression of beta-catenin, a coactivator of canonical Wnt pathways, was increased in PDLSCs with fucoidan. beta-catenin was found to link with PI3K activation during the fucoidan stimulation. When cells were blocked by PI3K inhibitor or beta-catenin-specific siRNA, fucoidan-induced osteogenic activity of PDLSCs was significantly attenuated. Conclusion: These findings suggest that the fucoidan stimulates osteogenic differentiation of PDLSCs via the PI3K/Akt and Wnt/beta-catenin pathways.