Wang Feng, Yin Peipei, Lu Ye, Zhou Zubin, Jiang Chaolai, Liu Yingjie, Yu Xiaowei
Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Oncotarget. 2015 Nov 3;6(34):35496-508. doi: 10.18632/oncotarget.6072.
Oxidative stress is known to be involved in impairment of osteogenesis and age-related osteoporosis. Cordycepin is one of the major bioactive components of Cordyceps militaris that has been shown to exert antioxidant and anti-inflammatory activities. However, there are few reports available regarding the effects of cordycepin on osteogenesis and the underlying mechanism. In this study, we investigated the potential osteoprotective effects of cordycepin and its mechanism systematically using both in vitro model as well as in vivo mouse models. We discovered that hydrogen peroxide (H2O2)-induced inhibition of osteogenesis which was rescued by cordycepin treatment in human bone marrow mesenchymal stem cells (BM-MSCs). Cordycepin exerted its protective effects partially by increasing or decreasing expression of osteogenic and osteoclastogenesis marker genes. Treatment with cordycepin increased Wnt-related genes' expression whereas supplementation of Wnt pathway inhibitor reversed its protective effects. In addition, administration of cordycepin promoted osteogenic differentiation of BM-MSCs by reducing oxidative stress in both ovariectomized and aged animal models. Taken together, these results support the protective effects of cordycepin on oxidative stress induced inhibition of osteogenesis by activation of Wnt pathway.
已知氧化应激与成骨受损及年龄相关性骨质疏松症有关。虫草素是蛹虫草的主要生物活性成分之一，已显示具有抗氧化和抗炎活性。然而，关于虫草素对成骨作用及其潜在机制的报道较少。在本研究中，我们使用体外模型和体内小鼠模型系统地研究了虫草素的潜在骨保护作用及其机制。我们发现，在人骨髓间充质干细胞（BM-MSCs）中，过氧化氢（H2O2）诱导的成骨抑制作用可通过虫草素处理得到挽救。虫草素部分通过增加或减少成骨和破骨细胞生成标记基因的表达发挥其保护作用。虫草素处理可增加Wnt相关基因的表达，而补充Wnt通路抑制剂可逆转其保护作用。此外，在去卵巢和老龄动物模型中，给予虫草素可通过降低氧化应激促进BM-MSCs的成骨分化。综上所述，这些结果支持虫草素通过激活Wnt通路对氧化应激诱导的成骨抑制具有保护作用。
