中国骨质疏松杂志

Wnt信号通路中DKK1、β-catenin基因在绝经后女性2型糖尿病患者中的表达及与骨代谢关系的研究

Expression of DKK1 and β-catenin in Wnt signaling pathway in postmenopausal women with type 2 diabetes mellitus and their relationship with bone metabolism

DOI：10.3969/j.issn.1006.7108.2018.11.012

中文关键词: 绝经后女性 2型糖尿病 DKK1 β-catenin qRT-PCR 骨密度

英文关键词:postmenopausal women type 2 diabetes Dkk1, β-catenin qRT-PCR bone mineral density

基金项目:区域创新引导计划（2018BB040）；留学人员科技活动项目择优资助基金(2016LX009)；兵团中青年科技创新领军人才专项（2015BC001）

作者	单位
胡倩1 周琼2 李军1* 李思源3 胡颖4 李佳佳1	1.新疆石河子大学医学院第一附属医院内分泌代谢科，新疆石河子 832000 2.新疆第二师二十九团医院，新疆库尔勒 841000 3.新疆石河子大学医学院，新疆石河子 832000 4.新疆医科大学第四附属医院，新疆乌鲁木齐830000

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中文摘要:

目的探讨绝经后女性2型糖尿病（T2DM）患者Wnt信号通路中血清DKK1、β-catenin基因的表达及与骨代谢的关系。方法收集新疆石河子社区、医院病人中2型糖尿病（T2DM）与糖耐量正常(NGT）受试者各50例，记录其年龄、身高、体重等一般临床基线资料，全自动生化分析仪测定空腹血糖（FPG）、血钙（Ｃa）、血磷（Ｐ）等生化指标，高压液相色谱法测定糖化血红蛋白（HbA1c）；双能X线（DXA）法测定腰椎及股骨骨密度；采用荧光定量反转录聚合酶链式反应法（qRT-PCR）检测DKK1基因和β-catenin基因表达水平并进行统计分析。结果 ①对绝经后女性NGT组和T2DM组年龄以及体质指数（BMI）进行统计分析，组间均无统计学差异（P＞0.05），说明资料齐，具有可比性。②与NGT组相比，T2DM组糖代谢指标：空腹血糖（fasting plasma glucose，FPG）、果糖胺（froctosamine，FMN）、HbA1c水平增高（P＜0.01）；骨代谢指标：磷（P）水平增高（P＜0.01）。③T2DM组股骨（femur）骨密度（bone mineral density，BMD）较NGT组显著降低（P＜0.05）。④与NGT组相比，T2DM组外周血白细胞中DKK1基因表达水平为NGT组的5.99倍，β-catenin基因表达水平为NGT组的0.46倍。⑤β-catenin基因在绝经后女性T2DM组中的表达与P呈负相关关系且差异具有统计学意义（P＜0.05）。⑥以骨代谢指标（Ca、P、ALP）为应变量，以DKK1基因和β-catenin基因为自变量，进行多元线性回归分析，在T2DM组中，β-catenin基因进入以P为应变量的回归方程：Y=1.445 – 0.287X。结论绝经后女性T2DM患者Wnt信号通路表达异常，DKK1基因的高表达可能抑制了其下游通路的转导，从而导致β-catenin基因的低表达，致使该人群BMD水平的下降，进而参与骨质疏松（OP）的发生发展。

英文摘要:

Objective To investigate the expression of DKK1 and β-catenin gene in Wnt signaling pathway and the relationship with bone metabolism in postmenopausal women with type 2 diabetes mellitus (T2DM). Methods Fifty patients with type 2 diabetes (T2DM) and fifty patients with normal glucose tolerance (NGT) from the community and inpatient community in Shihezi, Xinjiang, were selected. Their clinical data such as age, height, and body weight were recorded. Fasting plasma glucose (FPG), serum calcium (Ca), phosphorus (P), and other biochemical indicators were measured using an automatic biochemical analyzer. HbA1c were measured with high pressure liquid chromatography. Dual energy X-ray (DEXA) was used for the determination of bone mineral density of the lumbar vertebrae and femur. The expression of Dkk1 and β-catenin gene was detected using qRT-PCR and compared between groups. Results ①Compared with NGT group, there was no significant difference in age and BMI between T2DM and postmenopausal women (P>0.05). ②Compared with NGT group, the levels of the glucose metabolism indexes, FPG (5.47 ± 0.73, 9.26 ± 2.38), FOC (239.74 ± 36.54, 337.66 ± 87.31), and HbA1c (6.23 ± 0.92, 8.70 ± 1.76) in T2DM group increased (P<0.01), and bone metabolism indicators, P (1.11 ± 0.12,1.24 ± 0.16) also increased (P<0.01). ③BMD of the femur in T2DM group was significantly lower than that in NGT group (P<0.05). ④Compared with NGT group, the expression level of Dkk1 gene in peripheral leukocytes in T2DM group was 5.99 times higher and β-catenin gene was 0.46 times of that in NGT group. ⑤The expression of β-catenin gene in the postmenopausal female T2DM group was negatively correlated with P, and the difference was statistically significant (P<0.05). ⑥Multivariate linear stepwise regression analysis was performed using bone metabolic markers (Ca, P, and ALP) as dependent variable and DKK1 and β-catenin as independent variables. In the T2DM group, β-catenin gene entry was caused by P and the regression equation for the variable, Y=1.445–0.287X. Conclusion The expression of Wnt signaling pathway is abnormal in postmenopausal women with T2DM. The high expression of Dkk1 gene may inhibit the transduction of its downstream pathway, leading to the low expression of β-catenin gene, resulting in the decrease of BMD level in this population, and then participating in the occurrence and development of osteoporosis (OP).

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