机构地区:[1]解放军第八二医院内分泌科,淮安医学硕士研究生223001 [2]第四军医大学西京医院内分泌科,西安710032
出 处:《医学研究生学报》2011年第1期29-33,共5页Journal of Medical Postgraduates
摘 要:目的护骨素(osteoprotegerin,OPG)和护骨素配体(osteoprotegerin ligand,OPGL)是新发现的肿瘤坏死因子家族成员,与肿瘤坏死因子相关凋亡诱导配体(tumor necrosis factor-related apoptosis-inducing ligand,TRAIL)同为破骨细胞形成和活化的关键性调节因子。文中观察在不同浓度葡萄糖、雌二醇环境下人成骨肉瘤MG63细胞株中TRAIL及OPG、OPGL的表达,探讨绝经后糖尿病女性骨质疏松症的发病机制。方法用不同浓度葡萄糖(5.5、16.7、33.3 mmol/L)和雌二醇(17β-estradi-ol2,17β-E2)分别刺激培养的MG63细胞24 h,用MTT比色分析法测定细胞增殖,流式细胞仪检测细胞周期,RT-PCR法检测TRAIL、OPG、OPGLmRNA的表达。结果葡萄糖以浓度依赖方式抑制MG63细胞的增殖,并将细胞阻滞于G1期,葡萄糖对MG63细胞中TRAIL和OPGLmRNA表达的作用均依照对照组、葡萄糖5.5 mmol/L组、16.7 mmol/L组、33.3 mmol/L组顺序递增(P<0.05),而OPGmRNA的表达按照此顺序递减(P<0.05)。33.3 mmol/L组的TRAILmRNA水平明显高于对照组,分别为(1.004±0.070)和(0.740±0.023,P<0.05)。17β-E2可增加OPGmRNA的表达,减少TRAIL和OPGLmRNA的表达。结论高浓度葡萄糖可抑制成骨细胞的增殖,可能导致成骨细胞中TRAIL和OPGL表达增多,OPG的表达减少,导致骨质疏松。而雌激素可对高浓度葡萄糖环境下MG63细胞中TRAIL、OPG、OPGL的表达产生一定对抗效应,这可能是绝经后女性糖尿病患者合并骨质疏松症者施行雌激素替代治疗的依据之一。Objective Both osteoprotegerin(OPG) and the ligand of osteoprotegerin(OPGL) are tumor necrosis factors and,like the tumor necrosis factor-related apoptosis-inducing ligand(TRAIL),are also key regulators for the formation and activation of osteoclasts.This study was to observe the expressions of TRAIL,OPG and OPGL in osteosarcoma MG63 cells exposed to different concentrations of glucose and 17β-estradiol,and to investigate the pathogenesis of postmenopausal diabetic osteoporosis.Methods MG63 cells were incubated with different concentrations(5.5,16.7 and 33.3 mmol/L) of glucose and 17β-estradiol2(17β-E2) for 24 hours,respectively.The proliferation of osteoblasts was measured by antigenic MTT colorimetric analysis,their cell cycle determined by flow cytometry,and the mRNA expressions of TRAIL,OPG and OPGL detected by reverse transcriptase-PCR.Results Glucose inhibited the proliferation of the MG63 cells in a dose-dependent manner and arrested the cell cycle at the G1 phase.The mRNA expressions of TRAIL and OPGL in the MG63 cells were increased while that of OPG decreased progressively in the order of the control,5.5 mmol/L,16.7 mmol/L and 33.3 mmol/L groups(P0.05).The TRAIL mRNA level in the 33.3 mmol/L group was significantly higher than in the control(1.004±0.070 vs 0.740±0.023,P0.05).17β-E2 reduced the mRNA expressions of TRAIL and OPGL and increased that of OPG.Conclusion High-concentration glucose can suppress the proliferation of osteoblasts,increase the expressions of TRAIL and OPGL and decrease the expression of OPG in osteoblasts,and consequently induce diabetic osteoporosis.While 17β-estradiol has an antagonistic effect on the mRNA expressions of OPG,OPGL and TRAIL in the MG63 cells exposed to high-concentration glucose high glucose,which may be one of the mechanisms of 17β-estradiol replacement in the treatment of postmenopausal diabetic osteoporosis.
关 键 词:高糖 雌二醇 MG63细胞 肿瘤坏死因子相关凋亡诱导配体
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