Endothelial cells direct human mesenchymal stem cells for osteo- and chondro-lineage differentiation through endothelin-1 and AKT signaling.
Endothelial cells direct human mesenchymal stem cells for osteo- and chondro-lineage differentiation through endothelin-1 and AKT signaling.
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DOI：
10.1186/s13287-015-0065-6
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发表时间：
2015-05-01
影响因子：
7.5
通讯作者：
Li WJ
中科院分区：
文献类型：
--
作者：
Tsai TL;Wang B;Squire MW;Guo LW;Li WJ
Human mesenchymal stem cells (hMSCs) reside in a perivascular niche of the body, suggesting that they interact closely with vascular endothelial cells (ECs) through cell-cell interaction or paracrine signaling to maintain cell functions. Endothelin-1 (ET1) is a paracrine factor mainly secreted by ECs. We thus hypothesize that ECs can regulate cellular activities of hMSCs and direct their stem cell fate. We investigated whether co-cultured human aortic endothelial cells (HAECs) were able to regulate expression of potency- and lineage-related markers in bone marrow-derived hMSCs. We further explored the regulatory effects of ET1 on cell proliferation, expression of surface antigens and pluripotency-related markers, and multilineage differentiation in hMSCs. Activation of the AKT signaling pathway in hMSCs was also analyzed to identify its mechanistic role in the ET1-induced regulation. Co-cultured HAECs enhanced expression of mesenchymal lineage-related markers in hMSCs. Treatment of ET receptor antagonist downregulated the increased expression of CBFA1 in hMSCs cultured with HAEC-conditioned medium. hMSCs treated with ET1 showed cell proliferation and expression of surface antigens, CD73, CD90, and CD105, comparable with those without ET1 treatment. ET1-treated hMSCs also expressed upregulated mRNA transcript levels of OCT3/4, NANOG, CBFA1 and SOX9. When induced for lineage-specific differentiation, hMSCs pre-treated with ET1 showed enhanced osteogenesis and chondrogenesis. However, adipogenic differentiation of hMSCs was not affected by ET1 pretreatment. We further showed that the ET1-induced regulation was mediated by activation of AKT signaling. Our results demonstrate that ET1 secreted by HAECs can direct bone marrow-derived hMSCs for osteo- and chondro-lineage differentiation through activation of the AKT signaling pathway, suggesting that ET1 plays a crucial role in regulation of hMSC activity. Our findings may help understand how hMSCs interact with ECs in a perivascular niche. The online version of this article (doi:10.1186/s13287-015-0065-6) contains supplementary material, which is available to authorized users.
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影响因子：
5.2
作者：
Bartosh, Thomas J.;Yloestalo, Joni H.;Bazhanov, Nikolay;Kuhlman, Jessica;Prockop, Darwin J.
通讯作者：
Prockop, Darwin J.
DOI：
10.1073/pnas.1405388111
发表时间：
2014-07-15
影响因子：
11.1
作者：
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通讯作者：
Melero-Martin, Juan M.
影响因子：
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作者：
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通讯作者：
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影响因子：
6.5
作者：
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通讯作者：
Minguell, JJ
影响因子：
5.6
作者：
Cheng, Chin-Chang;Uchiyama, Yoshiyasu;Hiyama, Akihiko;Gajghate, Sachin;Shapiro, Irving M.;Risbud, Makarand V.
通讯作者：
Risbud, Makarand V.