High Glucose Potentiates Collagen Synthesis and Bone Morphogenetic Protein-2-Induced Early Osteoblast Gene Expression in Rat Spinal Ligament Cells
High Glucose Potentiates Collagen Synthesis and Bone Morphogenetic Protein-2-Induced Early Osteoblast Gene Expression in Rat Spinal Ligament Cells
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DOI：
10.1210/en.2009-0833
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发表时间：
2010-01-01
期刊：
影响因子：
4.8
通讯作者：
Dai, Li-Yang
中科院分区：
文献类型：
--
作者：
Li, Hai;Jiang, Lei-Sheng;Dai, Li-Yang
2型糖尿病（T2 DM）是后纵韧带骨化的独立危险因素，但其机制尚不清楚。我们从大鼠颈椎韧带中分离细胞，研究高糖对成骨细胞基因表达的影响，以提供深入的分子机制。使用这些细胞，高葡萄糖刺激I型胶原蛋白的合成，并显着增强骨形态发生蛋白-2（BMP-2）诱导的早期成骨细胞基因（Runx 2;碱性磷酸酶，ALP;和骨桥蛋白，OP）的表达。值得注意的是，高葡萄糖的这些作用被H2 O2完全模仿和增强，尽管被活性氧簇乙酰半胱氨酸阻断。此外，这些细胞暴露于高葡萄糖显着抑制p38 MAPK的磷酸化，同时增强细胞中蛋白激酶C（PKC）的磷酸化。与这些观察结果一致，p38抑制剂增强了高葡萄糖对BMP-2诱导的早期成骨基因表达的增强作用，而PKC抑制剂抑制了高葡萄糖对细胞I型胶原合成的影响。总之，高糖通过产生活性氧，随后激活PKC，抑制p38，增强I型胶原合成和BMP-2诱导的大鼠脊柱韧带细胞早期成骨基因的表达。高血压可能通过促进韧带细胞对成骨分化的反应性，在后纵韧带骨化的发生或进展中起重要作用。（内分泌学151：63-74，2010）
Type 2 diabetes mellitus (T2DM) is an independent risk factor for ossification of the posterior longitudinal ligament, but the mechanism is unclear. We isolated cells from rat cervical spine ligaments and studied the effects of high glucose on expression of osteoblast genes to provide insight into molecular mechanism. Using these cells, high glucose stimulated the synthesis of type I collagen and significantly potentiated expression of early osteoblast genes (Runx2; alkaline phosphatase, ALP; and osteopontin, OP) induced by bone morphogenetic protein-2 (BMP-2). Notably, these effects of high glucose were fully mimicked and augmented by H2O2, although blocked by the reactive oxygen species inhibitorN-acetyl cysteine. Furthermore, exposure of these cells to high glucose significantly suppressed the phosphorylation of p38MAPK while enhancing the phosphorylation of protein kinase C (PKC) in the cells. Consistent with these observations, an inhibitor of p38 augmented the potentiation of high glucose on BMP-2-induced early osteogenic gene expression, whereas the PKC inhibitor repressed the effect of high glucose on type I collagen synthesis of the cells. In conclusion, high glucose, via production of reactive oxygen species, subsequent activation of PKC, and inhibition of p38, enhances type I collagen synthesis and expression of early osteogenesis genes induced by BMP-2 in rat spinal ligament cells. Hyperglycemia may play an important role in the onset or progression of ossification of the posterior longitudinal ligament by promoting the responsiveness of ligament cells to osteogenic differentiation. (Endocrinology 151: 63-74, 2010)