Inhibition of PI3K/p70 S6K and p38 MAPK cascades increases osteoblastic differentiation induced by BMP-2
Inhibition of PI3K/p70 S6K and p38 MAPK cascades increases osteoblastic differentiation induced by BMP-2
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DOI：
10.1016/s0014-5793(01)03236-7
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发表时间：
2002-01-02
期刊：
影响因子：
3.5
通讯作者：
Ventura, F
中科院分区：
文献类型：
--
作者：
Viñals, F;López-Rovira, T;Ventura, F
骨形态发生蛋白（BMPs）可将C2Cl2细胞从肌源性谱系转分化为成骨性谱系。在这项工作中，我们研究了磷脂酰肌醇3-激酶/p70 S6激酶（PI3K/p70 S6K）和p38丝裂原活化蛋白激酶（p38 MAPK）级联在BMP-2成骨作用中的作用。BMP-2对这两个级联的刺激都是短暂的（在I h达到最大值，之后逐渐减小）。相比之下，BMP-2对p42/p44 MAPK （Erks）的刺激没有影响。我们还分析了这些途径的选择性抑制剂对成骨标志物表达的影响。p38 MAPK （SB203580）或PI3K/p70 S6K通路（Ly294002和雷帕霉素）的抑制剂不仅不能阻断BMP-2诱导的成骨细胞表型（通过诱导CUM表达和转录活性来测量），而且还能增强BMP-2对晚期成骨细胞标志物的影响，如碱性磷酸酶活性和骨钙素表达。这些数据表明，与其对成肌分化的积极作用相反，PI3K/p70 S6K和p38 MAPK级联在成骨细胞分化中具有消极作用。(C) 2002年由Elsevier Science B.V.代表欧洲生化学会联合会出版。
Bone morphogenetic proteins (BMPs) transdifferentiate C2Cl2 cells from the myogenic to the osteogenic lineage. In this work we examine the role of the phosphatidylinositol 3-kinase/p70 S6 kinase (PI3K/p70 S6K) and p38 mitogen-activated protein kinase (p38 MAPK) cascades in the osteogenic effects of BMP-2. BMP-2 stimulated both cascades transiently (maximal at I h and decreasing thereafter). In contrast, BMP-2 had no effect on p42/p44 MAPK (Erks) stimulation. We also analyzed the effects of selective inhibitors of these pathways on the expression of osteogenic markers. Inhibitors of p38 MAPK (SB203580) or the PI3K/p70 S6K pathway (Ly294002 and rapamycin) not only fail to block the osteoblast phenotype induced by BMP-2, measured as induction of CUM expression and transcriptional activity, but also potentiate the effect of BMP-2 on late osteoblast markers, such as alkaline phosphatase activity and osteocalcin expression. These data suggest that, in contrast to their positive effect on myogenic differentiation, PI3K/p70 S6K and p38 MAPK cascades have a negative role in osteoblast differentiation. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.