摘要
目的探讨PPAR72内源性配体氧化低密度脂蛋白(Ox-LDL)、15脱氧一前列腺素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24h,RT-PCR检测成骨细胞PPARγ2、NF-kB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PPARγ2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。
Objective To observe the effect of oxidized low-density lipoproteins (Ox-LDL), 15-Deoxy- △ 12,14.prostaglandin J2 ( 15d-PGJ2 ) , leukotrienes 114 ( LTB4 ) on mRNA expressions of peroxisome proliferator activated receptor γ2 ( PPART2 ), receptor activator of NF-KB 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, 50 μg/ml; the final concentrations of 15d-PGJ2 were 0, 10, 20, 30 μmol/L; the final concentrations of LTB4 were 0, O. 1, 1.0, 10 μmol/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 ceils 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.
出处
《中华内分泌代谢杂志》
CAS
CSCD
北大核心
2012年第3期221-225,共5页
Chinese Journal of Endocrinology and Metabolism
基金
山西省卫生厅科技攻关计划项目(200911)