Clinical Pharmacy of the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510060, China; School of Clinical Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
School of Clinical Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Carbohydr Polym. 2022 Jan 15;276:118730. doi: 10.1016/j.carbpol.2021.118730. Epub 2021 Oct 6.
Achyranthes bidentata is a traditional Chinese medicine used to treat osteoporosis. AB90, a crude saccharide from A. bidentata, showed excellent osteoprotective effects in ovariectomized rats, and ABW90-1, an oligosaccharide purified from AB90, stimulated significant differentiation of osteoblasts. However, the osteogenic effects and underlying mechanisms of ABW90-1 have remained unknown. In the present study, we found that ABW90-1 significantly promoted ALP activity, mineralization, and the expression of osteogenic markers in MC3T3-E1 cells. ABW90-1 showed strong binding with the WNT signaling complex and BMP2 based on number of interactions, hydrogen bond length, and binding energy in silico. ABW90-1 significantly increased the expression of active-β-catenin, p-GSK-3β, LEF-1, BMP2, and p-SMAD1. Importantly, the osteogenic effects of ABW90-1 were partially suppressed by DKK-1 and Noggin, which are specific inhibitors of the WNT and BMP signaling pathways, respectively. Collectively, these findings suggest that ABW90-1 has osteogenic effects through crosstalk between WNT/β-catenin and BMP2/SMAD1 signaling pathways.
牛膝是一种传统的中药，用于治疗骨质疏松症。AB90，牛膝中的一种粗糖，在去卵巢大鼠中显示出极好的护骨作用，ABW90-1，一种从 AB90 中纯化的低聚糖，刺激成骨细胞的显著分化。然而，ABW90-1 的成骨作用及其潜在机制尚不清楚。在本研究中，我们发现 ABW90-1 能显著促进 MC3T3-E1 细胞中 ALP 活性、矿化和成骨标志物的表达。ABW90-1 在计算机模拟中与 WNT 信号复合物和 BMP2 具有很强的结合能力，基于相互作用的数量、氢键长度和结合能。ABW90-1 显著增加了活性-β-catenin、p-GSK-3β、LEF-1、BMP2 和 p-SMAD1 的表达。重要的是，WNT 和 BMP 信号通路的特异性抑制剂 DKK-1 和 Noggin 部分抑制了 ABW90-1 的成骨作用。总之，这些发现表明 ABW90-1 通过 WNT/β-catenin 和 BMP2/SMAD1 信号通路的串扰发挥成骨作用。
