Peng Xiaoming, He Jichen, Zhao Jinmin, Wu Yunle, Shi Xiongzhi, Du Li, Nong Mengni, Zong Shaohui, Zeng Gaofeng
1 Department of Spine Osteopathia, The First Affiliated Hospital of Guangxi Medical University , Nanning, China .
2 Department of Osteopathia, the First Affiliated Hospital of Guangxi Medical University , Nanning, China .
Rejuvenation Res. 2018 Feb;21(1):44-52. doi: 10.1089/rej.2017.1956. Epub 2017 Aug 3.
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.
天然化合物黄精多糖(PSP)具有多种生物学作用,如降血脂、抗肿瘤、抗氧化活性以及增强免疫功能。我们之前的研究表明,PSP可通过增加β-连环蛋白的核内积累来促进骨髓间充质干细胞向成骨细胞(OB)分化。本研究旨在探讨PSP能否通过有效激活独立于低密度脂蛋白受体相关蛋白5(LRP5)的Wnt信号通路来上调核β-连环蛋白,而抑制糖原合酶激酶3β(GSK-3β)活性可阻止这种上调。我们发现PSP降低了GSK-3β的水平,GSK-3β通过细胞外信号调节激酶(ERK)信号通路使核β-连环蛋白磷酸化并使其不稳定。综上所述,这些发现表明PSP通过ERK/GSK-3β/β-连环蛋白信号通路促进体外OB分化和矿化。本研究可能有助于开发利用PSP增强骨骼健康和预防骨质疏松症的治疗方法。