Gene expression changes in cancellous bone of type 2 diabetics: a biomolecular basis for diabetic bone disease
Gene expression changes in cancellous bone of type 2 diabetics: a biomolecular basis for diabetic bone disease
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DOI：
10.1007/s00423-014-1188-4
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发表时间：
2014-06-01
影响因子：
2.3
通讯作者：
Freude, T.
中科院分区：
文献类型：
--
作者：
Haug, A. T.;Braun, K. F.;Freude, T.
2型糖尿病（2DM）与骨质改变有关。为了从分子水平上分析相关变化，我们研究了2型糖尿病患者成骨细胞代谢关键因子的基因表达，分离了2型糖尿病患者和非糖尿病患者的骨标本的总mRNA和蛋白，随后进行了逆转录聚合酶链反应（RT-PCR）或Western blot。此外，使用细胞因子阵列测定促炎和抗炎血清细胞因子水平，侏儒相关转录因子2（RUNX 2）的表达增加了53%。与对照组相比，研究糖尿病组中骨唾液酸蛋白、分泌磷蛋白1（SPP 1;骨桥蛋白）和整合素结合唾液酸蛋白（IBSP）的表达升高了50%以上，活化转录因子4（ATF 4）的表达降低了13%。同样，糖尿病组中多功能蛋白聚糖（VCAN）和核心蛋白聚糖（DCN）的表达上调了两倍。同时，2型糖尿病患者和对照组血清中促炎细胞因子和抗炎细胞因子水平发生改变，本研究发现2型糖尿病患者骨组织中转录因子和细胞外基质（ECM）成分的表达发生了相当大的变化。此外，成骨细胞的关键分化因子的分析显示，这些因素的基因表达的显着改变，这可能有助于在2 DM的能量代谢失调。
Diabetes mellitus type 2 (2DM) is associated with altered bone quality. In order to analyze associated changes on a molecular level, we investigated the gene expression of key factors of osteoblast metabolism in type 2 diabetics.Total mRNA and protein of bone samples from 2DM patients and non-diabetic patients were isolated, and subsequently, reverse transcription polymerase chain reaction (RT-PCR) or Western blot was performed. Furthermore, pro- and anti-inflammatory serum cytokine levels were determined using a cytokine array.Expression of runt-related transcription factor 2 (RUNX2) was increased by 53 %. Expression of the bone sialoproteins, secreted phosphoprotein 1 (SPP1; osteopontin), and integrin-binding sialoprotein (IBSP), was elevated by more than 50 %, and activating transcription factor 4 (ATF4) expression was 13 % lower in the investigated diabetes group compared to the control group. Similarly, the expression of versican (VCAN) and decorin (DCN) was upregulated twofold in the diabetic group. At the same time, 2DM patients and controls show alterations in pro- and anti-inflammatory cytokine levels in the serum.This study identifies considerable changes in the expression of transcription factors and extracellular matrix (ECM) components of bone in 2DM patients. Furthermore, the analysis of key differentiation factors of osteoblasts revealed significant alterations in gene expression of these factors, which may contribute to the dysregulation of energy metabolism in 2DM.