Lamin A overexpression promotes osteoblast differentiation and calcification in the MC3T3-E1 preosteoblastic cell line.
Lamin A overexpression promotes osteoblast differentiation and calcification in the MC3T3-E1 preosteoblastic cell line.
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DOI：
10.1016/j.bbrc.2017.02.110
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发表时间：
2017-07
影响因子：
3.1
通讯作者：
Naoya Tsukune;M. Naito;Tatsuya Kubota;Y. Ozawa;Mayu Nagao;Akiko Ohashi;Shuichi Sato;Tomihisa Takahashi
中科院分区：
文献类型：
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作者：
Naoya Tsukune;M. Naito;Tatsuya Kubota;Y. Ozawa;Mayu Nagao;Akiko Ohashi;Shuichi Sato;Tomihisa Takahashi
层粘连蛋白A/C是核层的一种成分，参与细胞的增殖和分化。然而，层蛋白A调节成骨细胞分化的机制还不是很清楚。在这项研究中，我们研究了成骨前细胞系MC3T3-E1成骨分化过程中层蛋白A/C的表达。实时荧光定量聚合酶链式反应分析显示，在BMP-2诱导成骨细胞分化过程中，Lamin A/C基因表达上调。雌激素受体拮抗剂fulvestrant可抑制成骨细胞分化，并在BMP-2存在的情况下上调lamin A/C的mRNA和蛋白表达。这些结果清楚地表明层蛋白A/C的表达与成骨细胞的分化有关。为探讨LAMIN A表达在成骨细胞分化中的作用，将LAMIN A高表达载体导入MC3T3-E1细胞，结果表明LAMIN A过表达通过诱导碱性磷酸酶、1型胶原、BSP、骨钙素和DMP-1的表达促进成骨细胞的分化和钙化。此外，层蛋白A的过度表达通过增加BSP、骨钙素和DMP-1的表达，部分恢复了在弗维斯特存在下的成骨能力。这些结果提示，层蛋白A在维持成骨细胞分化和功能中起着重要作用。
Lamin A/C is a component of the nuclear lamina, which is involved in cellular proliferation and differentiation. However, the mechanism by which lamin A regulates osteoblast differentiation is not well understood. In this study, we investigated lamin A/C expression during osteoblast differentiation in a preosteoblastic cell line, MC3T3-E1. Real-time PCR analysis showed that lamin A/C mRNA expression was upregulated during BMP-2 induced osteoblast differentiation. Treatment with the estrogen receptor antagonist, fulvestrant, inhibited osteoblast differentiation and the upregulation of lamin A/C mRNA and protein expressions in the presence of BMP-2. These results clearly demonstrated that lamin A/C expression correlates with osteoblast differentiation. To determine the roles of lamin A expression in osteoblast differentiation, MC3T3-E1 cells were transfected with a vector overexpressing lamin A. Results showed that lamin A overexpression promoted osteoblast differentiation and calcification by inducing the expression ofalkaline phosphatase,type 1 collagen,BSP,osteocalcin, andDMP-1in the presence of BMP-2. Furthermore, lamin A overexpression partially restored osteoblastic capacity in the presence of fulvestrant by increasing the expression ofBSP,osteocalcin, andDMP-1. These results suggest that lamin A plays important roles in maintaining the osteoblast differentiation and function.