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原发性纤毛调控人脐带来源间充质干细胞成脂分化过程中钙诱导的 Wnt5a/β-catenin 信号通路。

Primary Cilia Mediate Wnt5a/β-catenin Signaling to Regulate Adipogenic Differentiation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Following Calcium Induction.

机构信息

Biomedical Research Institute, MEDIPOST Co. Ltd, 21, Daewangpangyo-ro 644-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13494, Korea.

出版信息

Tissue Eng Regen Med. 2020 Apr;17(2):193-202. doi: 10.1007/s13770-019-00237-4. Epub 2020 Feb 1.

DOI:10.1007/s13770-019-00237-4
PMID:32008170
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7105559/
Abstract

BACKGROUND

Regeneration of soft tissue defects is essential for adipose tissue pathologies and disease, trauma, or injury-induced damage. Here, we show that umbilical cord blood-derived mesenchymal stem cells could potentially be tailored and used for the reconstruction of specific damaged sites. Adipogenesis can be exploited in soft tissue reconstruction. Also, primary cilia play a role in the control of adipogenesis.

METHODS

The adipogenic differentiation capacity of mesenchymal stem cells (MSCs) was shown to influence ciliogenesis. MSCs transfected with intraflagellar transport 88 (IFT88) small interfering RNA (siRNA), which blocks the assembly and maintenance of cilia, were examined to confirm the relationship between adipogenesis and ciliogenesis. Also, 1,2-Bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA-AM), calcium chelator, inhibited the ciliogenesis of MSCs in adipogenic differentiation.

RESULTS

IFT88-knockdown led to decreased cilia formation and limitation of cilia elongation in adipogenesis. Additionally, intracellular calcium triggered cilia formation in MSCs adipogenesis. Interestingly, intracellular calcium cannot overcome the inhibition of adipogenesis caused by low numbers of cilia in MSCs.

CONCLUSION

Our data suggested that ciliogenesis was negatively regulated by Wnt5a/β-catenin signaling during adipogenesis. Thus, we suggest that calcium induction triggers adipogenesis and ciliogenesis.

摘要

背景

软组织缺损的再生对于脂肪组织病理学、疾病、创伤或损伤引起的损伤至关重要。在这里,我们表明脐带血衍生的间充质干细胞可以被定制并用于特定受损部位的重建。脂肪生成可用于软组织重建。此外,初级纤毛在脂肪生成的控制中发挥作用。

方法

证明间充质干细胞(MSCs)的脂肪生成分化能力会影响纤毛发生。转染了内鞭毛运输 88(IFT88)小干扰 RNA(siRNA)的 MSCs 被检查以确认脂肪生成和纤毛发生之间的关系,IFT88 siRNA 阻止纤毛的组装和维持。此外,1,2-双(2-氨基苯氧基)乙烷-N,N,N',N'-四乙酸四(乙酰氧甲基酯)(BAPTA-AM),钙螯合剂,抑制了 MSCs 在脂肪生成分化中的纤毛发生。

结果

IFT88 敲低导致脂肪生成中纤毛形成减少和纤毛伸长受限。此外,细胞内钙在 MSCs 脂肪生成中触发纤毛形成。有趣的是,细胞内钙不能克服 MSCs 中纤毛数量少引起的脂肪生成抑制。

结论

我们的数据表明,在脂肪生成过程中,纤毛发生受到 Wnt5a/β-catenin 信号的负调控。因此,我们建议钙诱导触发脂肪生成和纤毛发生。

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本文引用的文献

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Umbilical cord as a long-term source of activatable mesenchymal stromal cells for immunomodulation.脐带作为一种可激活的间充质基质细胞的长期来源,用于免疫调节。
Stem Cell Res Ther. 2019 Sep 23;10(1):285. doi: 10.1186/s13287-019-1376-9.
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Adipogenesis for soft tissue reconstruction.用于软组织重建的脂肪生成。
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The nuclear receptor RXRA controls cellular senescence by regulating calcium signaling.核受体 RXRA 通过调节钙信号控制细胞衰老。
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Deficient primary cilia in obese adipose-derived mesenchymal stem cells: obesity, a secondary ciliopathy?肥胖脂肪来源间充质干细胞中初级纤毛缺失:肥胖,一种继发性纤毛病?
Obes Rev. 2018 Oct;19(10):1317-1328. doi: 10.1111/obr.12716. Epub 2018 Jul 17.
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Role of cord blood and bone marrow mesenchymal stem cells in recent deep burn: a case-control prospective study.脐血和骨髓间充质干细胞在近期深度烧伤中的作用:一项病例对照前瞻性研究。
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