摘要目的 探讨PPARγ2内源性配体氧化低密度脂蛋白(Ox-LDL)、15脱氧-前列腺素J2( 15d-PGJ2)、白三烯B4(LTB4)在骨代谢中的作用.方法 体外培养大鼠成骨细胞,分别加入不同浓度Ox-LDL、15d-PGJ2、LTB4干预24 h,RT-PCR检测成骨细胞PPARγ2、NF-κB活化受体配体(RANKL)、碱性磷酸酶(ALP)、护骨素mRNA表达水平,分别比较上述3种PPAR-γ2内源性配体对骨代谢相关基因表达的影响.结果 不同浓度Ox-LDL、15d-PGJ2、LTB4均呈剂量依赖性下调成骨细胞RANKL、ALP、护骨素mRNA的表达水平,同时呈剂量依赖性上调PPARγ2 mRNA的表达水平,组间比较差异有统计学意义(P＜0.05或P＜0.01).结论 PPARγ2内源性活化配体Ox-LDL、15d-PGJ2、LTB4可能通过激活PPARγ2转录活性抑制成骨细胞成骨标记物基因的表达,从而参与增龄相关的骨质疏松的发病过程.

abstractsObjective To observe the effect of oxidized low-density lipoproteins (Ox-LDL),15-Deoxy-△ 12,14-prostaglandin J2 ( 15d-PGJ2 ),leukotrienes B4 ( LTB4 ) on mRNA expressions of peroxisome proliferator activated receptor γ2 ( PPARγ2 ),receptor activator of NF-κB ligand (RANKL),alkaline phosphatase ( ALP),and osteoprotegerin(OPG) in osteoblastic cells of rats; and to investigate the influence of these PPARγ2 endogenous ligands on bone metabolism.Methods Rat osteoblastic cells were cultured in vitro for 24 h in medium with different PPARγ2 endogenous ligands at various concentrations ( the final concentrations of Ox-LDL were 0,12.5,25,50μg/ml; the final concentrations of 15 d-PGJ2 were 0,10,20,30 μmol/L; the final concentrations of LTB4 were 0,0.1,1.0,10 μ mol/L).RT-PCR was performed to determine the mRNA expressions of PPARγ2,RANKL,ALP,and OPG in osteoblastic cells.Results RT-PCR analysis showed that Ox-LDL,15d-PGJ2,and LTB4 all down-regulated the mRNA expressions of RANKL,ALP,and OPG,while up-regulated the mRNA expressions of PPARγ2 in osteoblastic cells in a dose-dependent manner.Significant differences were found in interclass comparisons( P＜0.05 or P＜ 0.01 ).Conclusions These findings suggest that Ox-LDL,15d-PGJ2,and LTB4 suppress the expressions of osteogenic genes through activating the transcription activity of PPARγ2,and this may be a plausible mechanism of senile osteoporosis.