Cryptochrome 1 Regulates Osteoblast Differentiation via the AKT Kinase and Extracellular Signal-Regulated Kinase Signaling Pathways.

Cryptochrome 1 Regulates Osteoblast Differentiation via the AKT Kinase and Extracellular Signal-Regulated Kinase Signaling Pathways.
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DOI:
10.1089/cell.2018.0054
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发表时间:
2019-05
影响因子:
1.6
通讯作者:
Lei Zhou;Jun He;Shiwei Sun;Yue-Ming Yu;Tie-Qi Zhang;Minghai Wang
Lei Zhou;Jun He;Shiwei Sun;Yue-Ming Yu;Tie-Qi Zhang;Minghai Wang
中科院分区:
医学4区
文献类型:
--
作者:
Lei Zhou;Jun He;Shiwei Sun;Yue-Ming Yu;Tie-Qi Zhang;Minghai Wang

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许多生物钟基因建立了一个网络结构,控制睡眠周期、新陈代谢和激素分泌等生理过程。隐花色素1(Cryptochrome 1,CR 1)是一种重要的昼夜节律蛋白,与骨形成密切相关。然而,在成骨分化的调节功能,resistance 1仍不清楚。在这项研究中,我们研究了在C3 H10和C2 C12细胞中,使用短发夹RNA干扰沉默Cry 1后,Cry 1在调节增殖和成骨细胞分化中的作用。体外实验证实,Cry 1在成骨分化过程中表达水平逐渐升高,Cry 1敲低抑制成骨细胞的增殖和分化。此外,Cry 1基因敲低可抑制AKT激酶(AKT)和细胞外信号调节激酶(ERK)的磷酸化,从而抑制磷脂酰肌醇-4,5-二磷酸3-激酶(PI 3 K)-AKT和丝裂原活化蛋白激酶(MAPK)-ERK信号通路。综上所述,这些发现表明,ARM 1调节成骨细胞的增殖和分化的AKT和ERK依赖的方式。
The many circadian clock genes build up a network structure that controls physiological processes, such as the sleep cycle, metabolism, and hormone secretion. Cryptochrome 1 (CRY1), as one of the critical circadian proteins, is closely related to bone formation. However, the regulatory function of CRY1 in osteogenic differentiation remains unclear. In this study, we investigated the role of CRY1 in regulating proliferation and osteoblast differentiation in C3H10 and C2C12 cells after silencing Cry1 using short hairpin RNA interference. In vitro experiments confirmed that the expression level of CRY1 gradually increased during the osteogenic differentiation process, and Cry1 knockdown inhibited the proliferation and differentiation of osteoblastic cells. In addition, Cry1 knockdown inhibited the phosphorylation of AKT kinase (AKT) and extracellular signal-regulated kinase (ERK), which suppressed the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT and mitogen-activated protein kinase (MAPK)-ERK signaling pathways. Taken together, these findings show that CRY1 regulates the proliferation and differentiation of osteoblastic cells in an AKT and ERK-dependent manner.