Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling.

Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling.
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DOI:
10.1083/jcb.200401138
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发表时间:
2004-07-05
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Komori T
Komori T
中科院分区:
其他
文献类型:
--
作者:
Fujita T;Azuma Y;Fukuyama R;Hattori Y;Yoshida C;Koida M;Ogita K;Komori T

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Runx 2和磷脂酰肌醇3-激酶(PI 3 K)-Akt信号在成骨细胞和软骨细胞分化中起重要作用。我们研究了Runx 2与PI 3 K-Akt信号通路之间的关系。Runx 2的强制表达增强了C3 H10 T1/2和MC 3 T3-E1细胞的成骨分化,增强了ATDC 5细胞的软骨分化,而这些作用被IGF-I抗体或LY 294002或显性阴性(dn)-Akt的腺病毒引入阻断。Runx 2或dn-Runx 2的强制表达分别增强或抑制细胞迁移,而Runx 2的增强作用被LY 294002或腺病毒导入dn-Akt所消除。Runx 2上调PI 3 K亚基(p85和p110β)和Akt,其表达模式与Runx 2相似。LY 294002处理或引入dn-Akt严重降低Runx 2和Runx 2依赖性转录的DNA结合,而myrAkt的强制表达增强了它们。这些发现表明Runx 2和PI 3 K-Akt信号在成骨细胞和软骨细胞分化及其迁移的调节中相互依赖。
Runx2 and phosphatidylinositol 3-kinase (PI3K)–Akt signaling play important roles in osteoblast and chondrocyte differentiation. We investigated the relationship between Runx2 and PI3K-Akt signaling. Forced expression of Runx2 enhanced osteoblastic differentiation of C3H10T1/2 and MC3T3-E1 cells and enhanced chondrogenic differentiation of ATDC5 cells, whereas these effects were blocked by treatment with IGF-I antibody or LY294002 or adenoviral introduction of dominant-negative (dn)–Akt. Forced expression of Runx2 or dn-Runx2 enhanced or inhibited cell migration, respectively, whereas the enhancement by Runx2 was abolished by treatment with LY294002 or adenoviral introduction of dn-Akt. Runx2 up-regulated PI3K subunits (p85 and p110β) and Akt, and their expression patterns were similar to that of Runx2 in growth plates. Treatment with LY294002 or introduction of dn-Akt severely diminished DNA binding of Runx2 and Runx2-dependent transcription, whereas forced expression of myrAkt enhanced them. These findings demonstrate that Runx2 and PI3K-Akt signaling are mutually dependent on each other in the regulation of osteoblast and chondrocyte differentiation and their migration.
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