Exogenous Heparan Sulfate Enhances the TGF-β3-Induced Chondrogenesis in Human Mesenchymal Stem Cells by Activating TGF-β/Smad Signaling
Exogenous Heparan Sulfate Enhances the TGF-β3-Induced Chondrogenesis in Human Mesenchymal Stem Cells by Activating TGF-β/Smad Signaling
复制标题
外源硫酸乙酰肝素通过激活 TGF-β/Smad 信号传导增强人间充质干细胞中 TGF-β 3 诱导的软骨形成
DOI：
10.1155/2016/1520136
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发表时间：
2016-01-01
影响因子：
4.3
通讯作者：
Xu, Caixia
中科院分区：
文献类型：
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作者：
Chen, Juan;Wang, Yongqian;Xu, Caixia
硫酸乙酰肝素（HS）与生长因子相互作用，并参与调节软骨形成。然而，HS对tgf - β介导的间充质干细胞（MSC）软骨形成的影响及其分子机制尚不清楚。在这项研究中，我们探讨了外源性HS单独和联合tgf - β 3对人MSCs软骨分化的影响和可能的信号机制。结果表明，HS单独对人MSCs的成软骨分化及tgf - β /Smad2/3信号通路无明显影响。然而，与单独使用tgf - β 3处理的细胞相比，tgf - β 3/HS联合处理导致GAG合成、软骨基质蛋白分泌和软骨特异性基因表达显著增加。此外，HS抑制了III型tgf - β受体（T β RIII）的表达，增加了tgf - β 3介导的II型（T β RII）与I型（T β RI） tgf - β受体的比例和Smad2/3的磷酸化水平。tgf - β /Smad信号抑制剂SB431542不仅完全抑制HS刺激的tgf - β 3介导的Smad2/3磷酸化，而且完全抑制HS对tgf - β 3诱导的软骨分化的影响。这些结果表明，外源性HS通过激活tgf - β /Smad2/3信号，增强tgf - β 3诱导的人间充质干细胞的软骨分化。
Heparan sulfate (HS) interacts with growth factors and has been implicated in regulating chondrogenesis. However, the effect of HS on TGF-beta-mediated mesenchymal stem cell (MSC) chondrogenesis and molecular mechanisms remains unknown. In this study, we explored the effects of exogenous HS alone and in combination with TGF-beta 3 on chondrogenic differentiation of human MSCs and possible signal mechanisms. The results indicated that HS alone had no obvious effects on chondrogenic differentiation of human MSCs and TGF-beta/Smad2/3 signal pathways. However, the combined TGF-beta 3/HS treatment resulted in a significant increase in GAG synthesis, cartilage matrix protein secretion, and cartilage-specific gene expression compared to cells treated with TGF-beta 3 alone. Furthermore, HS inhibited type III TGF-beta receptors (T beta RIII) expression and increased TGF-beta 3-mediated ratio of the type II (T beta RII) to the type I (T beta RI) TGF-beta receptors and phosphorylation levels of Smad2/3. The inhibitor of the TGF-beta/Smad signal, SB431542, not only completely inhibited HS-stimulated TGF-beta 3-mediated Smad2/3 phosphorylation but also completely inhibited the effects of HS on TGF-beta 3-induced chondrogenic differentiation. These results demonstrate exogenous HS enhances TGF-beta 3-induced chondrogenic differentiation of human MSCs by activating TGF-beta/Smad2/3 signaling.