Lactoferrin promotes MC3T3-E1 osteoblast cells proliferation via MAPK signaling pathways
Lactoferrin promotes MC3T3-E1 osteoblast cells proliferation via MAPK signaling pathways
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DOI：
10.1016/j.ijbiomac.2017.08.151
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发表时间：
2018-02-01
影响因子：
8.2
通讯作者：
Du, Ming
中科院分区：
文献类型：
--
作者：
Liu, Meng;Fan, Fengjiao;Du, Ming
乳铁蛋白具有多种生物活性，作为一种潜在的预防骨质疏松症的功能因子引起了人们的极大关注。然而，乳铁蛋白成骨活性的分子机制尚不清楚。本研究采用四甲基偶氮唑盐比色法检测乳铁蛋白对MC3T3-E1成骨细胞增殖的影响，并基于MAPK信号转导通路的mRNA和蛋白表达水平，探讨MAPK信号转导途径对MC3T3-E1成骨细胞增殖的影响。流式细胞仪检测细胞在不同细胞周期中的分布。结果表明，乳铁蛋白以剂量依赖的方式促进成骨细胞的增殖：即增加细胞处于S和G2/M期的比例。此外，我们还发现乳铁蛋白可以激活ERK、JNK和p38MAPK。经乳铁蛋白处理后，MAPK的mRNA表达明显增强。乳铁蛋白显著促进ERK和p38MAPK的激活相关磷酸化，并抑制JNK的激活。此外，乳铁蛋白还可使c-Fos和c-jun的表达分别增加3倍和26倍。这些结果表明乳铁蛋白通过刺激ERK、JNK和p38，通过c-Fos和c-jun诱导MC3T3-E1成骨细胞的增殖，阐明了乳铁蛋白对MC3T3-E1成骨细胞的成骨作用的分子基础。(C)2017爱思唯尔B.V.保留所有权利。
Lactoferrin has attracted great attention as a potential functional factor to prevent osteoporosis due to its various bioactivities. However, the molecular mechanism underlining the osteogenic activity of lactoferrin is unclear. In this study, effect of lactoferrin on MC3T3-E1 osteoblast cells proliferation was determined using MTT assay, while MAPK signaling pathways related to proliferation of MC3T3-E1 osteoblast cells were investigated based on mRNA and protein expressions. The distribution of cells at different cell cycle stages was evaluated by flow cytometry. Our findings indicated that lactoferrin enhanced MC3T3-E1 osteoblast cells proliferation in a dose-dependent manner: namely, it increased the proportion of cells in S and G2/M phases. Furthermore, we also found that lactoferrin could stimulate ERK, JNK and p38 MAPK. The mRNA expression of MAPK were significantly enhanced after treatment of lactoferrin. Lactoferrin significantly promoted the activation-associated phosphorylation of ERK and p38 MAPK and prevented the activation of JNK. Additionally, lactoferrin could enhance c-Fos and c-Jun expression by 3 times and 26 times, respectively. These results indicated that lactoferrin induced MC3T3-E1 osteoblast cells proliferation through c-Fos and c-Jun by stimulating ERK, JNK and p38, elucidating the molecular basis of the osteogenic activity of lactoferrin on MC3T3-E1 osteoblast cells. (C) 2017 Elsevier B.V. All rights reserved.