白三烯B4对骨髓细胞及成骨细胞骨代谢相关基因mRNA表达的影响  

Influence of leukotrienes B4 on mRNA expression of PPARγ2 and bone metabolism related markers of bone marrow cells and osteoblastic cells

作　　者：朱亦堃[1] 李丽婷[2] 史书红[2] 郗光霞[2] 李兴[2] 赵宝珍[2] 

机构地区：[1]山西医科大学第二医院内分泌科,太原市030001 [2]山西医科大学2008级硕士研究生

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2010年第3期187-193,共7页Chinese Journal Of Osteoporosis And Bone Mineral Research

基　　金：山西省卫生厅科技攻关计划项目(200911)

摘　　要：目的观察不同浓度白三烯B4(LTB4)干预后大鼠骨髓细胞及成骨细胞过氧化物酶体增生物激活受体γ2(PPARγ2)及骨代谢相关基因核因子-KB活化受体配体(RANKL)、碱性磷酸酶(ALP)、骨保护素(OPG)、核因子-KB活化受体(RANK)和抗酒石酸酸性磷酸酶(TRAP)mRNA表达水平的变化,探讨PPARγ2内源性配体LTB4在骨代谢中的作用。方法体外培养大鼠骨髓细胞及成骨细胞,分别加入不同浓度LTB4(0、0.1、1.0、10.0μmol/L)干预24 h,采用逆转录PCR(RT-PCR)法检测骨髓细胞PPARγ2、RANKL、ALP、OPG、RANK、TRAP mRNA表达水平及成骨细胞PPARγ2、RANKL、ALP、OPG mRNA表达水平,比较不同浓度LTB4对上述基因表达的影响。结果 (1)不同浓度LTB4呈剂量依赖性下调骨髓细胞RANKL、ALP、OPG mRNA的表达水平,同时呈剂量依赖性上调PPARγ2、RANK、TRAP mRNA的表达水平,组间比较差异均有统计学意义(P<0.05,P<0.01);(2)不同浓度LTB4呈剂量依赖性下调成骨细胞RANKL、ALP、OPG mRNA的表达水平,同时呈剂量依赖性上调PPARγ2mRNA的表达水平,组间比较差异有统计学意义(P<0.05,P<0.01)。结论 LTB4可能通过激活PPARγ2转录活性抑制骨髓细胞及成骨细胞成骨标记物基因的表达,促进骨髓细胞破骨标记物基因的表达,从而参与与增龄相关的骨质疏松的发病过程。Objective To observe the effect of leukotrienes B4 （LTB4） on mRNA expression of peroxisome proliferator activated receptorsγ2 （PPARγ2） and bone metabolism related markers of bone marrow cells and osteoblastic cells of rats, and investigate the influence of LTB4 on bone metabolism. Methods Bone marrow cells and osteoblastic cells of rats were cultured in vitro and were then cultured for 24h in medium with LTB4 at different concentrations （ final concentration is 0, 0. 1, 1.0 and 10μmol/L, respectively） . RT-PCR was performed to semi-determine the mRNA expression of PPARγ2, RANKL, ALP, OPG, RANK, TRAP of bone marrow cells and the mRNA expression of PPARγ2, RANKL, ALP, OPG of osteoblastic cells. Results （ 1 ） Semi-quantitative RT-PCR analysis showed that LTB4 downregulated the mRNA expression of RANKL, ALP and OPG, while it up-regulated the mRNA expression of PPARγ2, RANK and TRAP of bone marrow cells in a dose-dependent manner. Statistical significance was found in interclass comparison （P 〈0. 05, P 〈0.01 ）. （2） It also showed that LTB4 down-regulated the mRNA expression of RANKL, ALP and OPG, while it up-regulated the mRNA expression of PPARγ2 of osteoblastic cells in a dose-dependent manner. Statistical significance was found in interclass comparison （P 〈 0.05, P 〈 0. 01 ）. Conclusion These findings suggest that LTB4 suppress the expression of osteogenic genes through activating the transcription activity of PPARγ2, while it promote the expression of osteoclastogenesis genes. And it may be a plausible mechanism of type II primary osteoporosis.

关 键 词：过氧化物酶体增生物激活受体Γ 白三烯B4 骨髓细胞 成骨细胞 骨质疏松 

分 类 号：R681[医药卫生—骨科学]