Natural compound polygonatum sibiricum polysaccharide (PSP) has a variety of biological actions such as reducing blood fat, antitumor and antioxidant activities, and enhancing immune function. Our previous study has revealed that PSP can promote osteoblastic (OB) differentiation in bone mesenchymal stem cells by increasing nuclear accumulation of β-catenin. This study was designed to investigate that PSP can upregulate nuclear β-catenin, which was prevented by inhibiting the glycogen synthase kinase 3β (GSK-3β) activity, by effectively activating Wnt signaling independent of low-density lipoprotein receptor-related protein 5 (LRP5). We showed that PSP reduced the level of GSK-3β, which phosphorylates and destabilizes nuclear β-catenin through extracellular signal-regulated kinase (ERK) signaling pathway. Taken together, these findings demonstrate that PSP promotes OB differentiation and mineralization in vitro through the ERK/GSK-3β/β-catenin signaling pathways. This study may aid in the development of a therapeutic approach utilizing PSP for the enhancement of bone health and prevention of osteoporosis.
Keywords: ERK/GSK-3β/β-catenin; LRP5; osteoporosis; polygonatum sibiricum polysaccharide.