期刊
JOURNAL OF BONE AND MINERAL RESEARCH
卷 25, 期 11, 页码 2470-2478出版社
WILEY
DOI: 10.1002/jbmr.163
关键词
SIMVASTATIN; MURINE EMBRYONIC STEM CELLS; OSTEOINDUCTION
资金
- Department of Trade and Industry UK
Statins are potent inhibitors of cholesterol synthesis Several statins are available with different molecular and pharmacokinetic properties Simvastatin is more lipophilic than pravastatin and has a higher affinity to phospholipid membranes than atorvastatin allowing its passive diffusion through the cell membrane In vitro studies on bone marrow stromal cells osteoblast like cells and embryonic stem cells have shown statins to have cholesterol independent anabolic effects on bone metabolism alas statins were supplemented in osteogenic medium which does not facilitate elucidation of their potential osteoinductive properties Embryonic stem cells (ESCs) derived from the inner cell mass of the blastocyst are unique in that they enjoy perpetual self proliferation are pluripotent and are able to differentiate toward all the cellular lineages composing the body including the osteogenic lineage Consequently, ESCs represent a potentially potent cell source for future clinical cellular therapies of various bone diseases even though there are several hurdles that still need to be overcome Herein we demonstrate for the first time to our knowledge that simvastatin induces murine ESC (mESC) differentiation toward the osteogenic lineage in the absence of osteoinductive supplements Specifically, we found that a simvastatin concentration in the micromolar range and higher was toxic to the cells and that an effective concentration for osteoinduction is 0 1 nM as shown by increased alizarin red staining as well as increased osteocalcin and osetrtx gene expression These results suggest that in the future lipophilic simvastatin may provide a novel pharmacologic agent for bone tissue engineering applications (C) 2010 American Society for Bone and Mineral Research
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据