PKR plays a positive role in osteoblast differentiation by regulating GSK-3 activity through a β-catenin-independent pathway.
PKR plays a positive role in osteoblast differentiation by regulating GSK-3 activity through a β-catenin-independent pathway.
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PKR 通过不依赖于 β-catenin 的途径调节 GSK-3 活性，从而在成骨细胞分化中发挥积极作用。
DOI：
10.1016/j.mce.2012.03.019
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发表时间：
2012
影响因子：
4.1
通讯作者：
Yoshida K et al.
中科院分区：
文献类型：
--
作者：
Fujino Yoko;Minamizaki Tomoko;Sakurai Kaoru;Irie Yasumasa;Yosioka Hirotaka;Takei Yuichiro;Kozai Katsuyuki;Okada Mitsugu;Yoshiko Yuji;Hoshino T;内藤 真理子;Yoshida K et al.
双链RNA依赖性蛋白激酶(PKR)参与多种细胞功能。我们之前报道过 PKR 调节成骨细胞分化，但其发生的具体机制仍不清楚。在本研究中，我们研究了 PKR 在糖原合酶激酶 3β (GSK-3β) 调节成骨细胞分化中的作用。氯化锂 (LiCl) 是一种 GSK-3β 抑制剂，可增加 MC3T3-E1 和 MG-63 细胞中 GSK-3β 的磷酸化。 LiCl 还抑制 Runx2 及其调节基因的表达，从而抑制碱性磷酸酶活性和矿化。向小鼠颅骨注射氯化锂可抑制骨形成。此外，成骨细胞中的 GSK-3β 磷酸化通过 Akt 独立机制增加，其中 PKR 被组成性失活。 PKR 抑制剂 2-氨基嘌呤也在 MC3T3-E1 和 MG-63 细胞中诱导 GSK-3β 磷酸化。此外，Runx2 及其调节基因在 PKR 失活的成骨细胞中受到抑制，并且通过不依赖 β-连环蛋白的途径抑制分化。 PKR 通过不依赖 β-连环蛋白的途径介导 GSK-3β 活性，从而正向调节成骨细胞的分化。
Double-stranded RNA-dependent protein kinase (PKR) is involved in various cellular functions. We previously reported that PKR regulates osteoblast differentiation, but the specific mechanisms by which this occurs remain unclear. In this study, we investigated the role of PKR in Glycogen synthase kinase 3β (GSK-3β) regulation of osteoblast differentiation. Lithium chloride (LiCl), a GSK-3β inhibitor, increased GSK-3β phosphorylation in MC3T3-E1 and MG-63 cells. LiCl also inhibited Runx2 and expression of its regulated genes, causing inhibition of Alkaline phosphatase activity and mineralization. LiCl injection to the calvaria in mice suppressed bone formation. Further, GSK-3β phosphorylation was increased in osteoblasts, by Akt-independent mechanisms, in which PKR was constitutively inactivated. A PKR inhibitor, 2-aminopurine, also induced GSK-3β phosphorylation in MC3T3-E1 and MG-63 cells. Further, Runx2 and its regulated genes were inhibited in PKR-inactivated osteoblasts, and differentiation was suppressed through a β-catenin-independent pathway. PKR positively regulates the differentiation of osteoblasts by mediating GSK-3β activity through a β-catenin-independent pathway.