Wu Yuqiong, Xia Lunguo, Zhou Yuning, Xu Yuanjin, Jiang Xinquan
Department of Prosthodontics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Oral Bioengineering and Regenerative Medicine Lab, Shanghai Research Institute of Stomatology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China.
Cell Prolif. 2015 Jun;48(3):375-84. doi: 10.1111/cpr.12185. Epub 2015 Apr 13.
Icariin, a flavonoid isolated from Epimedium pubescens, has previously been identified to exert beneficial effects on preventing bone loss and promoting bone regeneration. However, molecular mechanisms for its anabolic action have, up to now, remained largely unknown.
Effects of icariin on cell proliferation and osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs) were systematically evaluated. To characterize underlying mechanisms, its effects on mitogen-activated protein kinase (MAPK) signalling pathways were determined.
Results showed that icariin might not have enhanced effects on cell proliferation. However, it seemed to significantly enhance osteogenic differentiation of BMSCs, demonstrated by increasing alkaline phosphatase (ALP) activity and gene expression of collagen type I (Col I), osteocalcin (OCN) and osteopotin (OPN). It was demonstrated that icariin rapidly phosphorylated extracellular signal-regulated kinase (ERK), p38 kinase and c-Jun N terminal kinase (JNK). Furthermore, icariin-stimulated osteogenic effects on BMSCs were dramatically attenuated by treatment with either specific ERK inhibitor of PD98059, p38 inhibitor of SB202190 or JNK inhibitor SP600125.
These results provide a potential mechanism of anabolic activity of icariin on BMSCs involving ERK, p38 and JNK MAPK pathways.
淫羊藿苷是从柔毛淫羊藿中分离出的一种黄酮类化合物，此前已被证实对预防骨质流失和促进骨再生具有有益作用。然而，其合成代谢作用的分子机制至今仍 largely 未知。
系统评估了淫羊藿苷对大鼠骨髓间充质干细胞（BMSCs）细胞增殖和成骨分化的影响。为了阐明潜在机制，测定了其对丝裂原活化蛋白激酶（MAPK）信号通路的影响。
结果表明，淫羊藿苷可能对细胞增殖没有增强作用。然而，它似乎能显著增强 BMSCs 的成骨分化，这通过碱性磷酸酶（ALP）活性以及 I 型胶原蛋白（Col I）、骨钙素（OCN）和骨桥蛋白（OPN）基因表达的增加得以证明。已证实淫羊藿苷能迅速磷酸化细胞外信号调节激酶（ERK）、p38 激酶和 c-Jun N 末端激酶（JNK）。此外，用 PD98059（ERK 特异性抑制剂）、SB202190（p38 抑制剂）或 SP600125（JNK 抑制剂）处理可显著减弱淫羊藿苷对 BMSCs 的成骨刺激作用。
这些结果为淫羊藿苷对 BMSCs 的合成代谢活性提供了一种潜在机制，涉及 ERK、p38 和 JNK MAPK 信号通路。
