Haug A T, Braun K F, Ehnert S, Mayer L, Stöckle U, Nüssler A K, Pscherer S, Freude T
Dept. of Trauma Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Straße 22, 81675, Munich, Germany,
Langenbecks Arch Surg. 2014 Jun;399(5):639-47. doi: 10.1007/s00423-014-1188-4. Epub 2014 Apr 10.
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.
2型糖尿病（2DM）与骨质量改变有关。为了在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2DM患者和非糖尿病患者骨样本的总mRNA和蛋白质，随后进行逆转录聚合酶链反应（RT-PCR）或蛋白质印迹分析。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。
与对照组相比，2DM组中与 runt 相关的转录因子2（RUNX2）的表达增加了53%。骨唾液蛋白、分泌性磷蛋白1（SPP1；骨桥蛋白）和整合素结合唾液蛋白（IBSP）的表达升高超过50%，而激活转录因子4（ATF4）的表达降低了13%。同样，核心蛋白聚糖（VCAN）和饰胶蛋白聚糖（DCN）的表达在糖尿病组中上调了两倍。同时，2DM患者和对照组血清中促炎和抗炎细胞因子水平存在改变。
本研究确定了2DM患者骨转录因子和细胞外基质（ECM）成分表达的显著变化。此外，对成骨细胞关键分化因子的分析揭示了这些因子基因表达的显著改变，这可能导致2DM患者能量代谢失调。
