BACKGROUND & AIMS:
:Mechano-growth factor (MGF), a splice variant of insulin-like growth factor I (IGF-I), was discovered by Goldspink and colleagues in 1996; since then many studies have implicated MGF as an important local tissue repair factor. Although the short 24-amino-acid C-terminal peptide of MGF (MGF-Ct24E) has a variety of biological activities, its role in bone formation has not yet been clarified. Accordingly, the aim of this study was to investigate the role of MGF-Ct24E in the proliferation, differentiation, and mineralization of rat calvarial osteoblasts. Interestingly, although MGF-Ct24E significantly increased the proliferation and retarded the differentiation of osteoblasts during the first 3 days, prolonged treatment with MGF-Ct24E for up to 3 weeks promoted cell differentiation. To determine the molecular mechanisms behind this plurality, we carried out global transcriptional profiling of osteoblasts in response to MGF-Ct24E and identified differentially expressed genes by bioinformatics analysis. Gene ontology analysis indicated that MGF-Ct24E enhanced the expression of genes associated with osteoblast proliferation and the cell cycle and downregulated genes involved with osteoblast differentiation, skeletal system, and bone development. Moreover, KEGG pathway-based analysis indicated that MGF-Ct24E directly altered focal adhesion and cell cycle progression, in addition to regulating the actin cytoskeleton and gap junctions. In conclusion, MGF-Ct24E has a marked ability to increase bone formation by increasing cell proliferation and delaying cell differentiation during prophase, as well as by stimulating osteoblast differentiation during the advanced stage. The mechanism of action of MGF-Ct24E during the initial stages of bone formation in vitro involves upregulation of the expression of genes involved in proliferation and cell cycle progression, and the repression of differentiation-related genes.
背景与目标:
: 机械生长因子 (MGF) 是胰岛素样生长因子I (igf-i) 的剪接变体,由Goldspink及其同事1996年发现; 此后,许多研究表明MGF是重要的局部组织修复因子。尽管MGF (MGF-Ct24E) 的短24氨基酸C端肽具有多种生物学活性,但其在骨形成中的作用尚未阐明。因此,本研究的目的是研究MGF-Ct24E在大鼠颅骨成骨细胞增殖,分化和矿化中的作用。有趣的是,尽管MGF-Ct24E在最初的3天中显着增加了成骨细胞的增殖并延迟了成骨细胞的分化,但延长MGF-Ct24E治疗长达3周可促进细胞分化。为了确定这一多个背后的分子机制,我们对成骨细胞进行了整体转录分析,以响应MGF-Ct24E,并通过生物信息学分析鉴定了差异表达的基因。基因本体分析表明,MGF-Ct24E增强了与成骨细胞增殖和细胞周期相关的基因的表达,并下调了与成骨细胞分化,骨骼系统和骨骼发育有关的基因的表达。此外,基于KEGG途径的分析表明,除了调节肌动蛋白细胞骨架和间隙连接外,MGF-Ct24E还直接改变了黏着斑和细胞周期进程。总之,MGF-Ct24E具有通过在前期增加细胞增殖和延迟细胞分化以及在晚期刺激成骨细胞分化来增加骨形成的显著能力。在体外骨形成的初始阶段,MGF-Ct24E的作用机制涉及参与增殖和细胞周期进程的基因表达的上调以及分化相关基因的抑制。