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.

中文翻译：

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Cryptochrome 1通过AKT激酶和细胞外信号调节的激酶信号通路调节成骨细胞分化。

许多昼夜节律时钟基因建立了一个控制生理过程的网络结构，例如睡眠周期，新陈代谢和激素分泌。隐花色素1（CRY1）作为重要的昼夜节律蛋白质之一，与骨骼形成密切相关。但是，CRY1在成骨分化中的调控功能仍不清楚。在这项研究中，我们调查了使用短发夹RNA干扰沉默Cry1后CRY1在调节C3H10和C2C12细胞增殖和成骨细胞分化中的作用。体外实验证实，CRY1的表达水平在成骨分化过程中逐渐升高，而Cry1敲低抑制了成骨细胞的增殖和分化。此外，Cry1基因敲低抑制了AKT激酶（AKT）和细胞外信号调节激酶（ERK）的磷酸化，从而抑制了磷脂酰肌醇-4,5-双磷酸3-激酶（PI3K）-AKT和有丝分裂原激活的蛋白激酶（MAPK）-ERK信号通路。综上，这些发现表明，CRY1以AKT和ERK依赖性方式调节成骨细胞的增殖和分化。