Conditional tenomodulin overexpression favors tenogenic lineage differentiation of transgenic mouse derived cells
Conditional tenomodulin overexpression favors tenogenic lineage differentiation of transgenic mouse derived cells
复制标题
条件性肌腱调节蛋白过表达有利于转基因小鼠来源细胞的肌腱谱系分化
DOI：
10.1016/j.gene.2016.10.028
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发表时间：
2017-01-20
期刊：
影响因子：
3.5
通讯作者：
Liu, Wei
中科院分区：
文献类型：
--
作者：
Shi, Yuan;Xiong, Yao;Liu, Wei
Tenomodulin（TNMD）是一种II型跨膜蛋白，广泛表达于各种无血管结缔组织和脂肪组织中。除了成熟腱细胞的标记物外，其功能在很大程度上仍未知。本研究报告了四环素（泰特）驱动的条件TNMD过表达小鼠的产生，从而提供了一个工具，系统研究其在调节各种组织的功能。本研究旨在比较多西环素（Dox）对同一转基因小鼠骨髓源性干细胞（BMSCs）、脂肪源性干细胞（ASC）、真皮成纤维细胞（DF）和肌腱细胞（TC）的体外诱导分化潜能。结果显示，BMSCs表现出最好的成腱潜能（大多数标记物p < 0.05），而ASCs和DF表现出相似的潜能（大多数标记物p > 0.05）。TC被发现最不能够被诱导tenogenic基因表达。此外，TNMD过表达还显著抑制BMSCs和ASCs向成骨和软骨细胞系的分化（p < 0.05）。然而，在ASCs中未观察到脂肪形成分化的抑制（p>0.05），这表明不同的基因调控机制可能涉及不同的组织类型，从而导致不同的功能，这可能通过转基因小鼠模型来揭示。(C)2016爱思唯尔B.V.保留所有权利。
Tenomodulin (TNMD) is a type II transmembrane protein that is widely expressed in a variety of avascular connective tissues and fat tissue. Its function remains largely unknown except for a marker for mature tenocytes. This study reports the generation of tetracycline (Tet)-on driven conditional TNMD overexpressing mice and thus to provide a tool for systemic investigation of its role in regulating functions of various tissues. The current study focuses on in vitro comparison of tenogenic differentiation potentials induced by doxycycline (Dox) treatment among bone marrow derived stem cells (BMSCs), adipose derived stem cells (ASCs), dermal fibroblasts (DFs) and tenocytes (TCs) of the same transgenic mice. The results showed that BMSCs exhibited the best tenogenic potential than other three cell types (p < 0.05 for majority of markers), whereas ASCs and DFs revealed similar potentials (p > 0.05 for majority of markers). TCs were found the least capable of being induced for tenogenic gene expression. In addition, TNMD overexpression also significantly inhibited the differentiation towards osteogenic and chondrogenic lineages in both BMSCs and ASCs (p < 0.05). However, the inhibition of adipogenic differentiation was not observed in ASCs (p>0.05), suggesting different gene regulation mechanisms may involve in different tissue types and thus leading to different functions, which is likely to be revealed with a transgenic mouse model. (C) 2016 Elsevier B.V. All rights reserved.