1-(5-Oxohexyl)-3,7-Dimethylxanthine, a Phosphodiesterase Inhibitor, Activates MAPK Cascades and Promotes Osteoblast Differentiation by a Mechanism Independent of PKA Activation (Pentoxyfilline Promotes Osteoblast Differentiation).
1-(5-Oxohexyl)-3,7-Dimethylxanthine, a Phosphodiesterase Inhibitor, Activates MAPK Cascades and Promotes Osteoblast Differentiation by a Mechanism Independent of PKA Activation (Pentoxyfilline Promotes Osteoblast Differentiation).
复制标题
1-(5-Oxhexyl)-3,7-Dimethylxanthine 是一种磷酸二酯酶抑制剂，通过独立于 PKA 激活的机制激活 MAPK 级联并促进成骨细胞分化（喷托菲林促进成骨细胞分化）。
作者：
G. Rawadi;C. Ferrer;S. Spinella;S. Roman;Y. Bouali;R. Baron
我们已经研究了1-（5-氧代己基）-3，7-二甲基黄嘌呤或戊酰茶碱（PETx），一种非选择性磷酸二酯酶抑制剂，在体外成骨细胞分化的影响，通过使用两个间充质细胞系，C3 H10 T12和C2 C12，这是能够获得成骨细胞表型的骨形态发生蛋白-2（BMP-2）的存在下。在C3 H10 T12和C2 C12细胞中，PETx诱导成骨细胞标志物骨钙素和Osf 2/Cbfa 1，并增强BMP-2诱导的骨钙素、Osf 2/Cbfa 1和碱性磷酸酶的表达。这种活性部分归因于PeTx能够增强BMP-2诱导的Smad 1转录活性的事实。虽然PeTx清楚地刺激PKA在这些细胞中，既不预处理细胞与PKA抑制剂H89也不转染与特定的PKA抑制剂PKI阻止诱导或增强成骨细胞标志物的PeTx，表明这些效果是独立的PKA激活。另一方面，PeTx诱导ERK 1的激活。
We have investigated the effect of 1-(5-oxohexyl)-3,7-dimethylxanthine or pentoxifylline (PeTx), a nonselective phosphodiesterase inhibitor, on osteoblastic differentiation in vitro by using two mesenchymal cell lines, C3H10T1/2 and C2C12, which are able to acquire the osteoblastic phenotype in the presence of bone morphogenetic protein-2 (BMP-2). PeTx induced the osteoblastic markers, osteocalcin and Osf2/Cbfa1, in C3H10T1/2 and C2C12 cells and enhanced BMP-2-induced expression of osteocalcin, Osf2/Cbfa1, and alkaline phosphatase. This activity was partially attributed to the fact that PeTx is able to enhance BMP-2-induced Smad1 transcriptional activity. Although PeTx clearly stimulates PKA in these cells, neither pretreatment of cells with the PKA inhibitor H89 nor transfection with the specific PKA inhibitor PKI prevented the induction or enhancement of osteoblast markers by PeTx, demonstrating that these effects were independent of PKA activation. On the other hand, PeTx induced the activation of ERK1...