Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul 02453, Republic of Korea.
National Institute for Korean Medicine Development, Gyeongsan 38540, Republic of Korea.
Am J Chin Med. 2021;49(4):883-900. doi: 10.1142/S0192415X21500427. Epub 2021 Apr 7.
L. (Rosaceae) is a perennial herbaceous plant and its roots have been used as an important traditional medicine for over 2000 years. Ziyuglycoside I (Ziyu), an active compound isolated from the roots of L., has shown biological effects such as anti-oxidant, antiviral, and antiwrinkle activities. This study aimed to elucidate the underlying mechanisms of action of Ziyu on cytotoxicity, migration, and differentiation of pre-osteoblasts. Herein, at concentrations ranging from 1 to 100 [Formula: see text]M, Ziyu was not cytotoxic against pre-osteoblasts. Alkaline phosphatase activity assay and staining, and migration assay showed that Ziyu increased cell migration and promoted early osteoblast differentiation, followed by the enhancement of mineralized nodule formation in a dose-dependent manner, as indicated by Alizarin Red S staining. In addition, Ziyu increased the protein levels of runt-related transcription factor 2 (RUNX2) during osteoblast differentiation, whereas it did not affect the phosphorylation of Smad1/5/8 and GSK3b and expression of [Formula: see text]-catenin. Ziyu also activated ERK1/2 and mitogen-activated protein kinase during osteoblast differentiation, and ERK1/2 inhibitor attenuated Ziyu-mediated RUNX2 expression and nuclear accumulation. Furthermore, Ziyu-mediated early and late osteoblast differentiation was significantly suppressed by the inhibition of ERK1/2, which was accompanied by attenuation in the mRNA levels of osteoblast-related genes including bone sialoprotein, osteopontin, and osteocalcin. Taken together, the findings of this study provide evidence that Ziyu promotes cell migration, osteoblast differentiation, and bone mineralization and suggest a potential role for Ziyu in the treatment of bone diseases.
（蔷薇科）是一种多年生草本植物，其根已被用作重要的传统药物超过 2000 年。从 （蔷薇科）根部分离得到的活性化合物梓醇（Ziyu）具有抗氧化、抗病毒和抗皱等生物活性。本研究旨在阐明 Ziyu 对前成骨细胞细胞毒性、迁移和分化的作用机制。在此，在 1 至 100 [Formula: see text]M 的浓度范围内，Ziyu 对前成骨细胞无细胞毒性。碱性磷酸酶活性测定和染色以及迁移测定表明，Ziyu 以剂量依赖性方式增加细胞迁移并促进早期成骨细胞分化，随后增强矿化结节形成，茜素红 S 染色表明。此外，Ziyu 在成骨细胞分化过程中增加 runt 相关转录因子 2（RUNX2）的蛋白水平，而不影响 Smad1/5/8 和 GSK3b 的磷酸化和 [Formula: see text]-连环蛋白的表达。Ziyu 还在成骨细胞分化过程中激活 ERK1/2 和丝裂原活化蛋白激酶，而 ERK1/2 抑制剂减弱了 Ziyu 介导的 RUNX2 表达和核积累。此外，Ziyu 介导的早期和晚期成骨细胞分化被 ERK1/2 的抑制显著抑制，伴随着骨唾液蛋白、骨桥蛋白和骨钙素等成骨细胞相关基因的 mRNA 水平降低。总之，本研究结果提供了证据表明 Ziyu 促进细胞迁移、成骨细胞分化和骨矿化，并表明 Ziyu 在治疗骨疾病方面具有潜在作用。
