TZDs对骨髓破骨细胞生成作用和成骨细胞生成作用的影响Effects of TZDs on osteoblastogenesis and osteoclastogenesis in primary bone marrow cell
黄仕龙;徐飞;董永辉;郭风劲;陈安民;许涛;
摘要(Abstract):
[目的]体外观察TZDs类药物对小鼠原代骨髓细胞向成骨细胞和破骨细胞分化的影响,探讨其对糖尿病患者骨骼代谢的影响和作用机制。[方法]无菌条件下从小鼠股骨分离获取骨髓细胞,贴壁细胞进行成骨细胞生成实验研究,悬浮细胞进行破骨细胞生成实验研究。随后在1、2、5μmol/L罗格列酮干预下诱导成骨细胞分化培养3周,进行Von Kossa染色观察成骨细胞矿化结节,并测定成骨细胞标记物ALP活性、BMP-2及TGF-β分泌的影响;观察罗格列酮对破骨细胞形成和成熟的影响及标志性基因表达。[结果]1、2、5μmol/L罗格列酮干预组与对照组相比,成骨细胞的钙结节形成比例显著降低(P<0.05),ALP、BMP-2、TGF-β水平呈剂量依赖性地下降(均P<0.05);同时剂量依赖性促进c-fos和RANK基因的表达,破骨细胞生成实验显示罗格列酮促进破骨细胞分化发育和成熟。[结论]罗格列酮可剂量依赖性地抑制骨髓细胞向成骨细胞分化,促进向破骨细胞分化。有助于理解Ⅱ型糖尿病患者在应用TZDs骨丢失的原因。
关键词(KeyWords): 罗格列酮;成骨细胞;破骨细胞;糖尿病骨代谢
基金项目(Foundation): 国家自然科学基金资助项目(编号:81070691)
作者(Authors): 黄仕龙;徐飞;董永辉;郭风劲;陈安民;许涛;
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