Type III Transforming Growth Factor-β Receptor RNA Interference Enhances Transforming Growth Factor β3-Induced Chondrogenesis Signaling in Human Mesenchymal Stem Cells.

Type III Transforming Growth Factor-β Receptor RNA Interference Enhances Transforming Growth Factor β3-Induced Chondrogenesis Signaling in Human Mesenchymal Stem Cells.
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III 型转化生长因子-β 受体 RNA 干扰增强人间充质干细胞中转化生长因子-β 3 诱导的软骨形成信号传导

DOI:
10.1155/2018/4180857
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发表时间:
2018
影响因子:
4.3
通讯作者:
Xu C
Xu C
中科院分区:
医学3区
文献类型:
--
作者:
Zheng S;Zhou H;Chen Z;Li Y;Zhou T;Lian C;Gao B;Su P;Xu C

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III型转化生长因子-β (TGF-β)受体(t -β riii)是TGF-β超家族的一种辅助受体,已知可结合TGF-βs并调节TGF-β信号传导。然而,t -β riii在TGF-β诱导的间充质干细胞(MSC)软骨形成中的调节作用尚未探讨。本研究探讨了t -β riii RNA干扰(RNAi)对TGF-β3诱导的人MSC (hMSC)软骨形成的影响及可能的信号机制。构建含有TβRIII小干扰RNA (siRNA) (SiTβRIII)或对照siRNA (SiNC)基因的慢病毒表达载体,并将其感染到hMSCs中。细胞在含TGF-β3的成软骨培养基或对照培养基中培养。与SiNC感染的细胞相比,TβRIII RNAi显著增强TGF-β3诱导的hMSCs成软骨分化、II型(TβRII)与I型(TβRI) TGF-β受体的比例以及Smad2/3的磷酸化水平。SB431542是一种TGF-β信号抑制剂,不仅抑制TβRIII RNAi刺激的TGF-β3介导的Smad2/3磷酸化,而且抑制TβRIII RNAi对TGF-β3诱导的软骨分化的作用。这些结果表明,t -β riii RNAi通过激活TGF-β/Smad2/3信号通路,增强TGF-β3诱导的hMSCs成软骨分化。这一发现指出了通过敲低TβRIII修饰MSCs作为未来基于细胞的软骨组织工程的有效策略的可能性。
The type III transforming growth factor-β (TGF-β) receptor (TβRIII), a coreceptor of the TGF-β superfamily, is known to bind TGF-βs and regulate TGF-β signaling. However, the regulatory roles of TβRIII in TGF-β-induced mesenchymal stem cell (MSC) chondrogenesis have not been explored. The present study examined the effect of TβRIII RNA interference (RNAi) on TGF-β3-induced human MSC (hMSC) chondrogenesis and possible signal mechanisms. A lentiviral expression vector containing TβRIII small interfering RNA (siRNA) (SiTβRIII) or a control siRNA (SiNC) gene was constructed and infected into hMSCs. The cells were cultured in chondrogenic medium containing TGF-β3 or control medium. TβRIII RNAi significantly enhanced TGF-β3-induced chondrogenic differentiation of hMSCs, the ratio of type II (TβRII) to type I (TβRI) TGF-β receptors, and phosphorylation levels of Smad2/3 as compared with cells infected with SiNC. An inhibitor of the TGF-β signal, SB431542, not only inhibited TβRIII RNAi-stimulated TGF-β3-mediated Smad2/3 phosphorylation but also inhibited the effects of TβRIII RNAi on TGF-β3-induced chondrogenic differentiation. These results demonstrate that TβRIII RNAi enhances TGF-β3-induced chondrogenic differentiation in hMSCs by activating TGF-β/Smad2/3 signaling. The finding points to the possibility of modifying MSCs by TβRIII knockdown as a potent future strategy for cell-based cartilage tissue engineering.
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