CD105 promotes chondrogenesis of synovium-derived mesenchymal stem cells through Smad2 signaling

CD105 promotes chondrogenesis of synovium-derived mesenchymal stem cells through Smad2 signaling
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CD105通过Smad2信号促进滑膜来源的间充质干细胞的软骨形成

DOI:
10.1016/j.bbrc.2016.04.101
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发表时间:
2016-05-27
影响因子:
3.1
通讯作者:
Yan, Zuoqin
Yan, Zuoqin
中科院分区:
生物学4区
文献类型:
--
作者:
Fan, Wenshuai;Li, Jinghuan;Yan, Zuoqin

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间充质干细胞(MSC)被认为是适合于基于细胞的组织再生。不同细胞表面标志物的表达赋予不同MSC亚群不同的分化潜能。了解细胞表面标志物对MSC分化的影响对于它们在不同组织中的靶向应用至关重要。虽然CD 105阳性的MSCs具有很强的成软骨能力,但其机制尚不清楚。在这项研究中,我们观察到相当大的异质性,从滑膜分离的MSC之间的CD 105表达。对CD 105(+)和CD 105(-)滑膜来源的MSC(SMSCs)进行分选,以比较其分化能力和相关基因表达。与CD 105(-)细胞相比,CD 105(+)细胞AGG、COL II和Sox 9基因表达水平较高,对阿辛蓝的亲和力较强,对聚集蛋白聚糖和胶原酶II的免疫荧光染色较强。而ALP、Runx 2、LPL和PPARy基因表达无显著差异。CD 105(+)SMSCs显示Smad 2磷酸化水平增加,而两组之间的总Smad 2水平相似。Smad 1/5的激活没有差异。这些结果通过SMSC中的CD 105敲低进一步证实。我们的研究结果表明,与CD 105(-)SMSCs相比,CD 105(+)SMSCs具有更强的软骨形成潜力,并且CD 105通过调节TGF-β/Smad 2信号通路而不是Smad 1/5来增强SMSCs的软骨形成。我们的研究提供了一个更好的理解CD 105与软骨分化。(C)2016 Elsevier Inc. All rights reserved.
Mesenchymal stem cells (MSCs) are considered to be suitable for cell-based tissue regeneration. Expressions of different cell surface markers confer distinct differentiation potential to different sub populations of MSCs. Understanding the effect of cell surface markers on MSC differentiation is essential to their targeted application in different tissues. Although CD105 positive MSCs possess strong chondrogenic capacity, the underlying mechanisms are not clear. In this study, we observed a considerable heterogeneity with respect to CD105 expression among MSCs isolated from synovium. The CD105(+) and CD105(-) synovium-derived MSCs (SMSCs) were sorted to compare their differentiation capacities and relative gene expressions. CD105(+) subpopulation had higher gene expressions of AGG, COL II and Sox9, and showed a stronger affinity for Alcian blue and immunofluorescent staining for aggrecan and collagenase II, as compared to those in CD105(-) cells. However, no significant difference was observed with respect to gene expressions of ALP, Runx2, LPL and PPARy. CD105(+) SMSCs showed increased levels of Smad2 phosphorylation, while total Smad2 levels were similar between the two groups. There was no difference in activation of Smad1/5. These results were further confirmed by CD105-knockdown in SMSCs. Our findings suggest a stronger chondrogenic potential of CD105(+) SMSCs in comparison to that of CD105(-) SMSCs and that CD105 enhances chondrogenesis of SMSCs by regulating TGF-beta/Smad2 signaling pathway, but not Smad1/5. Our study provides a better understanding of CD105 with respect to chondrogenic differentiation. (C) 2016 Elsevier Inc. All rights reserved.