Aluminum Trichloride Inhibited Osteoblastic Proliferation and Downregulated the Wnt/β-Catenin Pathway
Aluminum Trichloride Inhibited Osteoblastic Proliferation and Downregulated the Wnt/β-Catenin Pathway
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三氯化铝抑制成骨细胞增殖并下调 Wnt/β-Catenin 通路
DOI：
10.1007/s12011-016-0880-3
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发表时间：
2017-06-01
影响因子：
3.9
通讯作者：
Zhu, Yanzhu
中科院分区：
文献类型：
--
作者：
Huang, Wanyue;Wang, Peiyan;Zhu, Yanzhu
铝 (Al) 暴露会抑制骨形成。成骨细胞增殖促进骨形成。因此，我们推测Al可能通过抑制成骨细胞增殖来抑制骨形成。然而，Al对成骨细胞增殖的影响和分子机制仍在研究中。成骨细胞增殖可通过Wnt/β-catenin信号通路进行调节。为了研究Al对成骨细胞增殖的影响以及Wnt/β-catenin信号通路是否参与其中，培养新生大鼠的成骨细胞，并分别暴露于0、0.4 mM (1/20 IC50)、0.8 mM (1/10 IC50)和1.6 mM (1/5 IC50)的三氯化铝(AlCl3) 24 h。成骨细胞增殖率； Wnt3a、脂蛋白受体相关蛋白 5 (LRP-5)、T 细胞因子 1 (TCF-1)、细胞周期蛋白 D1 和 c-Myc 信使 RNA (mRNA) 表达； p-糖原合成酶激酶 3 beta (GSK3 beta)、GSK3 beta 和 beta-catenin 蛋白表达表明 AlCl3 抑制成骨细胞增殖并下调 Wnt/beta-catenin 信号通路。此外，AlCl3浓度与成骨细胞增殖率及Wnt3a、c-Myc、cyclin D1 mRNA表达量呈负相关，而成骨细胞增殖率与Wnt3a、c-Myc、cyclin D1 mRNA表达量呈正相关。综上所述，这些结果表明AlCl3抑制成骨细胞增殖可能与Wnt/β-catenin信号通路的失活有关。
Aluminum (Al) exposure inhibits bone formation. Osteoblastic proliferation promotes bone formation. Therefore, we inferred that Al may inhibit bone formation by the inhibition of osteoblastic proliferation. However, the effects and molecular mechanisms of Al on osteoblastic proliferation are still under investigation. Osteoblastic proliferation can be regulated by Wnt/beta-catenin signaling pathway. To investigate the effects of Al on osteoblastic proliferation and whether Wnt/beta-catenin signaling pathway is involved in it, osteoblasts from neonatal rats were cultured and exposed to 0, 0.4 mM (1/20 IC50), 0.8 mM (1/10 IC50), and 1.6 mM (1/5 IC50) of aluminum trichloride (AlCl3) for 24 h, respectively. The osteoblastic proliferation rates; Wnt3a, lipoprotein receptor-related protein 5 (LRP-5), T cell factor 1 (TCF-1), cyclin D1, and c-Myc messenger RNA (mRNA) expressions; and p-glycogen synthase kinase 3 beta (GSK3 beta), GSK3 beta, and beta-catenin protein expressions indicated that AlCl3 inhibited osteoblastic proliferation and downregulated Wnt/beta-catenin signaling pathway. In addition, the AlCl3 concentration was negatively correlated with osteoblastic proliferation rates and the mRNA expressions of Wnt3a, c-Myc, and cyclin D1, while the osteoblastic proliferation rates were positively correlated with mRNA expressions of Wnt3a, c-Myc, and cyclin D1. Taken together, these findings indicated that AlCl3 inhibits osteoblastic proliferation may be associated with the inactivation of Wnt/beta-catenin signaling pathway.