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三氯化铝通过抑制 Wnt/β-连环蛋白信号通路抑制大鼠成骨细胞的成骨分化。

Aluminum trichloride inhibits osteoblastic differentiation through inactivation of Wnt/β-catenin signaling pathway in rat osteoblasts.

机构信息

College of Veterinary Medicine, Northeast Agricultural University, NO. 59 Mucai Street, Xiangfang District, Harbin 150030, China.

College of Veterinary Medicine, Northeast Agricultural University, NO. 59 Mucai Street, Xiangfang District, Harbin 150030, China.

出版信息

Environ Toxicol Pharmacol. 2016 Mar;42:198-204. doi: 10.1016/j.etap.2015.11.023. Epub 2015 Dec 8.

Abstract

Exposure to aluminum (Al) suppresses bone formation. Osteoblastic differentiation plays a key role in the process of bone formation. However, the effect of Al on osteoblastic differentiation is still controversial, and the mechanism remains unclear. To investigate the effect of Al on osteoblastic differentiation and whether Wnt signaling pathway was involved in it, the primary rat osteoblasts were exposed to 1/40 IC50, 1/20 IC50 and 1/10 IC50 of aluminum trichloride (AlCl3) for 24h, respectively. The activity analysis of alkaline phosphate, qRT-PCR analysis of type I collagen, alkaline phosphate, Wnt3a and Dkk-1, Western blot analysis of p-GSK3β, GSK3β and β-catenin protein and Immunofluorescence staining for β-catenin suggested that AlCl3 inhibited osteoblastic differentiation and Wnt/β-catenin pathway. Moreover, we found exogenous Wnt3a application reversed the inhibitory effect of AlCl3 on osteoblastic differentiation, accompanied by activating the Wnt/β-catenin pathway. Taken together, these findings suggest that AlCl3 inhibites osteoblastic differentiation through inactivation of Wnt/β-catenin pathway in osteoblasts.

摘要

铝(Al)暴露会抑制骨形成。成骨细胞分化在骨形成过程中起着关键作用。然而,铝对成骨细胞分化的影响仍存在争议,其机制尚不清楚。为了研究铝对成骨细胞分化的影响,以及 Wnt 信号通路是否参与其中,将原代大鼠成骨细胞分别暴露于氯化铝(AlCl3)的 1/40IC50、1/20IC50 和 1/10IC50 下 24 小时。碱性磷酸酶活性分析、I 型胶原、碱性磷酸酶、Wnt3a 和 Dkk-1 的 qRT-PCR 分析、p-GSK3β、GSK3β 和 β-连环蛋白蛋白的 Western blot 分析以及β-连环蛋白的免疫荧光染色表明 AlCl3 抑制成骨细胞分化和 Wnt/β-连环蛋白通路。此外,我们发现外源性 Wnt3a 的应用逆转了 AlCl3 对成骨细胞分化的抑制作用,同时激活了 Wnt/β-连环蛋白通路。综上所述,这些发现表明 AlCl3 通过抑制成骨细胞中的 Wnt/β-连环蛋白通路来抑制成骨细胞分化。

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