The use of SHP-2 gene transduced bone marrow mesenchymal stem cells to promote osteogenic differentiation and bone defect repair in rat
The use of SHP-2 gene transduced bone marrow mesenchymal stem cells to promote osteogenic differentiation and bone defect repair in rat
复制标题
DOI：
10.1002/jbm.a.35718
复制
发表时间：
2016-08-01
影响因子：
4.9
通讯作者：
Fan, Cunyi
中科院分区：
文献类型：
--
作者：
Fan, Dapeng;Liu, Shen;Fan, Cunyi
骨组织工程是一种很有前途的骨再生方法，生长因子在其中起着重要的作用。PTPN11基因编码的蛋白酪氨酸磷酸酶2(SHP2)对成骨细胞的分化、增殖和代谢起着至关重要的作用。然而，SHP-2在成骨过程中的作用一直没有得到系统的研究。我们预测过表达SHP-2可以促进骨髓间充质干细胞(BMSC)的成骨分化，SHP-2转导的BMSCs可以促进新骨的形成。结果表明：(1)转导SHP-2的BMSCs+成骨诱导液(BMSCs/SHP-2/OL)；(2)转导SHP-2的BMSCs(BMSCs/-SHP-2)；(3)转导BMSCs+成骨诱导液(BMSCs/OL)和(4)纯BMSCs。采用实时定量聚合酶链式反应分析、免疫印迹分析、碱性磷酸酶活性和茜素红S染色等方法检测细胞成骨分化情况。为了进行体内评估，将细胞与β-磷酸三钙支架结合，移植到大鼠颅骨缺损处，为期8周。安乐死后，取颅骨标本进行成骨评价，包括显微计算机断层扫描测量、组织学和免疫组织化学染色。SHP-2及其基因的上调促进了BMSC的成骨分化，为骨修复提供了一种新的治疗途径。(C)2016 Wiley期刊，Inc.生物材料资源A部分：104A：1871-1881,2016。
Bone tissue engineering is a promising approach for bone regeneration, in which growth factors play an important role. The tyrosine phosphatase Src-homology region 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by the PTPN11 gene, is essential for the differentiation, proliferation and metabolism of osteoblasts. However, SHP-2 has never been systematically studied for its effect in osteogenesis. We predicted that overexpression of SHP-2 could promote bone marrow-derived mesenchymal stem cell (BMSC)osteogenic differentiation and SHP-2 transduced BMSCs could enhance new bone formation, determined using the following study groups: (1) BMSCs transduced with SHP-2 and induced with osteoblast-inducing liquid (BMSCs/SHP-2/OL); (2) BMSCs transduced with SHP-2 (BMSCs/-SHP-2); (3) BMSCs induced with osteoblast-inducing liquid (BMSCs/OL) and (4) pure BMSCs. Cells were assessed for osteogenic differentiation by quantitative real-time polymerase chain reaction analysis, western blot analysis, alkaline phosphatase activity and alizarin red S staining. For in vivo assessment, cells were combined with beta-tricalcium phosphate scaffolds and transplanted into rat calvarial defects for 8 weeks. Following euthanasia, skull samples were explanted for osteogenic evaluation, including micro-computed tomography measurement, histology and immunohistochemistry staining. SHP-2 and upregulation of its gene promoted BMSC osteogenic differentiation and therefore represents a potential new therapeutic approach to bone repair. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1871-1881, 2016.