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

作　　者：黄仕龙[1] 徐飞[1] 董永辉[1] 郭风劲[1] 陈安民[1] 许涛[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院骨外科,武汉430030 [2]华中科技大学同济医学院附属同济医院康复科,武汉430030

出　　处：《中国矫形外科杂志》2011年第19期1638-1641,共4页Orthopedic Journal of China

基　　金：国家自然科学基金资助项目(编号:81070691)

摘　　要：[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。[Objective]To investigate the ettects of TZDs on osteoclastogenesis and osteoblastogenesis of primary bone marrow cells,and address the mechanism of TZDs for bone metabolism of diabetics. [Methods]The bone marrow cells were obtained asepsisly from mouse femur and incubated overnight.The non-adherent cells were used for osteoclastogenesis assays and the adherent cells for osteoblastogenesis assays.CFU-OB,ALP activity and BMP-2,TGF-β were measured by Von Kossa,Western-blot assays after treated by rosiglitazone.Genes expression was tested by real time PCR. [Results]Compared with controls,CFU-OB decreased significantly in 1,2,5 μmol/L groups.ALP activity,BMP-2 and TGF-β expression were inhibited dose-dependently.On the other hand,rosiglitazone promoted osteoclastogenesis by up-regulation of the gene express of c-fos and RANK. [Conclusion]Rosiglitazone dose-dependently inhibits the differentiation of MSCs into osteoblasts but facilitates the differentiation of osteoclastogenesis.It helps us to understand the bone loss and osteoporosis in type 2 diabetes.

关 键 词：罗格列酮 成骨细胞 破骨细胞 糖尿病骨代谢 

分 类 号：R587.2[医药卫生—内分泌]