Primary Cilia Mediate Wnt5a/β-catenin Signaling to Regulate Adipogenic Differentiation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Following Calcium Induction
Primary Cilia Mediate Wnt5a/β-catenin Signaling to Regulate Adipogenic Differentiation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Following Calcium Induction
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DOI：
10.1007/s13770-019-00237-4
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发表时间：
2020-02-01
影响因子：
3.6
通讯作者：
Jin, Hye Jin
中科院分区：
文献类型：
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作者：
Bae, Yun Kyung;Kim, Gee-Hye;Jin, Hye Jin
背景：软组织缺损的再生是脂肪组织病理和疾病、创伤或损伤所必需的。在这里，我们展示了脐带血来源的间充质干细胞有可能被定制并用于特定受损部位的重建。成脂作用可用于软组织重建。此外，初级纤毛在控制脂肪生成方面也发挥了作用。方法：观察间充质干细胞(MSCs)的成脂分化能力对纤毛形成的影响。用鞭毛内转运88(IFT88)小干扰RNA(SiRNA)阻断纤毛的组装和维持，检测MSCs成脂和纤毛形成的关系。钙离子螯合剂1，2-双(2-氨基苯氧基)乙烷-N，N，N‘，N’-四乙酸四乙酸乙酯(BAPTA-AM)在成脂分化过程中抑制MSCs的纤毛发生。结果：在成脂过程中，IFT88基因敲除导致纤毛形成减少，纤毛伸长受限。此外，细胞内钙在MSCs的成脂过程中触发了纤毛的形成。有趣的是，细胞内钙不能克服骨髓间充质干细胞纤毛数量减少对脂肪生成的抑制。结论：Wnt5a/β-catenin信号在成脂过程中负向调控纤毛发生。因此，我们认为钙诱导可触发脂肪生成和纤毛生成。
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/beta-catenin signaling during adipogenesis. Thus, we suggest that calcium induction triggers adipogenesis and ciliogenesis.