Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul 02447, Korea.
Medical Device Research Center, Medical Science Research Institute, Kyung Hee University Medical Center, Seoul 02447, Korea.
Int J Mol Sci. 2021 Oct 21;22(21):11362. doi: 10.3390/ijms222111362.
Stem cells have received attention in various diseases, such as inflammatory, cancer, and bone diseases. Mesenchymal stem cells (MSCs) are multipotent stem cells that are critical for forming and repairing bone tissues. Herein, we isolated calycosin-7-O-β-glucoside (Caly) from the roots of , which is one of the most famous medicinal herbs, and investigated the osteogenic activities of Caly in MSCs. Caly did not affect cytotoxicity against MSCs, whereas Caly enhanced cell migration during the osteogenesis of MSCs. Caly increased the expression and enzymatic activities of ALP and the formation of mineralized nodules during the osteogenesis of MSCs. The osteogenesis and bone-forming activities of Caly are mediated by bone morphogenetic protein 2 (BMP2), phospho-Smad1/5/8, Wnt3a, phospho-GSK3β, and phospho-AKT, inducing the expression of runt-related transcription factor 2 (RUNX2). In addition, Caly-mediated osteogenesis and RUNX2 expression were attenuated by noggin and wortmannin. Moreover, the effects were validated in pre-osteoblasts committed to the osteoblast lineages from MSCs. Overall, our results provide novel evidence that Caly stimulates osteoblast lineage commitment of MSCs by triggering RUNX2 expression, suggesting Caly as a potential anabolic drug to prevent bone diseases.
干细胞在各种疾病中受到关注,如炎症、癌症和骨疾病。间充质干细胞(MSCs)是多能干细胞,对于形成和修复骨组织至关重要。在此,我们从 的根部分离出毛蕊异黄酮-7-O-β-葡萄糖苷(Caly),这是最著名的草药之一,并研究了 Caly 在 MSCs 中的成骨活性。Caly 对 MSCs 没有细胞毒性,而 Caly 增强了 MSCs 成骨过程中的细胞迁移。Caly 增加了 ALP 的表达和酶活性以及 MSCs 成骨过程中矿化结节的形成。Caly 通过骨形态发生蛋白 2(BMP2)、磷酸化 Smad1/5/8、Wnt3a、磷酸化 GSK3β 和磷酸化 AKT 介导成骨和骨形成活性,诱导 runt 相关转录因子 2(RUNX2)的表达。此外, noggin 和 wortmannin 减弱了 Caly 介导的成骨作用和 RUNX2 表达。此外,还在从 MSCs 定向成骨细胞系的前成骨细胞中验证了这些效果。总的来说,我们的结果提供了新的证据,表明 Caly 通过触发 RUNX2 表达刺激 MSCs 成骨谱系的承诺,表明 Caly 作为一种预防骨疾病的潜在合成代谢药物。