力生长因子及其E肽对成骨细胞分化的影响  

The Effects of MGF and E Peptide on The Differentiation of Osteoblasts

作　　者：张兵兵[1,2] 王远亮[1,2] 杨力[1,2] 潘长江[1,2] 傅亚[1,2] 邓墨渊[1,2] 李玉筱[1,2] 

机构地区：[1]重庆大学生物工程学院生物材料与仿生工程研究中心,重庆400044 [2]生物流变科学与技术教育部重点实验室(重庆大学),重庆400044

出　　处：《生物化学与生物物理进展》2010年第3期304-312,共9页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金资助项目(30870609)~~

摘　　要：力生长因子(mechano growth factor,MGF)是新近发现的一种生长因子,由Igf-1基因剪接变异产生,拉伸刺激会促使成骨细胞表达力生长因子.比较分析了MGF及其羧基端E肽(MGF-Ct24E)对成骨细胞前体细胞MC3T3-E1分化的影响.结果显示:MGF和MGF-Ct24E具有显著激活胞外信号调节激酶1/2(Erk1/2)的作用,并降低了成骨细胞碱性磷酸酶、Ⅰ型胶原的表达,促进了骨桥蛋白(OPN)的表达,减少了核心绑定因子(corebinding factor1,Cbfα-1)的核转运量,对成骨细胞的分化具有延迟效应,这种效应通过抑制剂PD98059抑制Erk1/2的活化得到逆转;MGF还能显著激活磷脂酰肌醇3-激酶信号通路中的蛋白激酶B(Akt),该活化作用对成骨细胞分化是必需的,钙沉积分析显示长期培养下的细胞MGF促进了矿化节结的形成.这些结果说明,MGF-Ct24E对成骨细胞的分化具有抑制作用,这种作用与Erk1/2的活化有关,MGF因为包含E肽和IGF-1部分,能分别激活Erk1/2和Akt,因此对成骨细胞分化表现出双重效用,在成骨细胞分化早期,具有一定的延迟效应,而在分化晚期对成骨细胞分化表现出促进作用.The mechano growth factor （MGF） is originated from alternative splicing of Igf-1 gene, which is mainly expressed in stretched osteoblasts. The main purpose of this study is to examine the effects of MGF and E peptide （the C-terminal 24 amino acids peptide in the E domain of MGF, MGF-Ct24E） on differentiation of osteoblast MC3T3-E1 cells. The results indicate that the MGF and MGF-Ct24E activated the extracellular signal-regulated kinase 1/2 （Erk1/2） and affected the expression of osteoblast-associated genes, including the reduced expression of alkaline phosphatase （ALP） and type 1 collagen （Col1）, the increased product of osteopontin （OPN） and the decreased nuclear levels of activated Cbfa-1. These effects could be abolished by the blockade of Erk1/2 activation by inhibitor PD98059. In addition, the MGF could preferably activate the PI3K-Akt pathway, which is essential for the differentiation of osteoblasts, so the osteoblast has higher expression of ALP, type 1 Col1, and the formation of bone mineralization nodule under the treatment of MGF than that under the treatment of MGF-Ct24E. These advantages could be inhibited after blockading of Akt by inhibitor LY294002. It was concluded that the MGF-Ct24E could inhibit osteoblasts differentiation through the activated Erk1/2 cascade, while the MGF can induce differentiation through the activated PI3K-Akt. The MGF consists of MGF-Ct24E and IGF-1, which could activate Erk1/2 and PI3K-Akt respectively. Therefore, the MGF possess double effects on differentiation of osteoblasts, which presented as that inhibitory effect at the early differentiation, and promoting effect at the later differentiation.

关 键 词：力生长因子 胰岛素样生长因子-1 成骨细胞 分化 

分 类 号：Q254[生物学—细胞生物学] R68[医药卫生—骨科学]