Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, South Korea.
Department of Preventive and Social Dentistry, School of Dentistry, Kyung Hee University, Seoul, South Korea.
Oral Dis. 2022 Sep;28(6):1628-1639. doi: 10.1111/odi.13829. Epub 2021 Mar 19.
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.
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.
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, p110α and p110γ compared to control cells. The phosphorylation of Akt, a PI3K downstream effector, was significantly increased at 90 min of fucoidan induction. Expression of β-catenin, a coactivator of canonical Wnt pathways, was increased in PDLSCs with fucoidan. β-catenin was found to link with PI3K activation during the fucoidan stimulation. When cells were blocked by PI3K inhibitor or β-catenin-specific siRNA, fucoidan-induced osteogenic activity of PDLSCs was significantly attenuated.
These findings suggest that the fucoidan stimulates osteogenic differentiation of PDLSCs via the PI3K/Akt and Wnt/β-catenin pathways.
背景/目的：褐藻糖胶作为一种多功能治疗药物，已被广泛应用于骨骼健康补充剂。然而，褐藻糖胶作为骨治疗药物的关键分子机制尚未完全阐明。本研究旨在探讨褐藻糖胶对牙周膜干细胞（PDLSCs）的成骨诱导作用及其促进 PDLSC 成骨的机制。
通过培养细胞并用褐藻糖胶处理来进行 PDLSCs 的成骨诱导。通过碱性磷酸酶（ALP）活性、基质矿化测定、细胞内钙水平以及成骨标志物的 mRNA 表达和蛋白水平来验证 PDLSCs 的成骨分化。
与对照组相比，褐藻糖胶处理组的 PDLSCs 表现出更高的成骨活性。与对照组细胞相比，褐藻糖胶处理的 PDLSCs 还表现出更高水平的磷脂酰肌醇-3-激酶（PI3K）同工型 p110α 和 p110γ。褐藻糖胶诱导 90 分钟后，Akt（PI3K 的下游效应物）的磷酸化水平显著增加。β-连环蛋白（经典 Wnt 途径的共激活因子）在褐藻糖胶处理的 PDLSCs 中的表达增加。在褐藻糖胶刺激期间发现β-连环蛋白与 PI3K 激活有关。当细胞被 PI3K 抑制剂或β-连环蛋白特异性 siRNA 阻断时，褐藻糖胶诱导的 PDLSCs 成骨活性显著减弱。
这些发现表明，褐藻糖胶通过 PI3K/Akt 和 Wnt/β-连环蛋白途径刺激 PDLSCs 的成骨分化。
