FOXQ1 promotes the osteogenic differentiation of bone mesenchymal stem cells via Wnt/β-catenin signaling by binding with ANXA2.
FOXQ1 promotes the osteogenic differentiation of bone mesenchymal stem cells via Wnt/β-catenin signaling by binding with ANXA2.
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FOXQ1 通过与 ANXA2 结合通过 Wnt/β-catenin 信号传导促进骨间充质干细胞的成骨分化
DOI：
10.1186/s13287-020-01928-9
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发表时间：
2020-09-17
影响因子：
7.5
通讯作者：
Cai B
中科院分区：
文献类型：
--
作者：
Xiang L;Zheng J;Zhang M;Ai T;Cai B
本研究探讨叉头盒Q1（FOXQ 1）在骨髓间充质干细胞成骨分化中的作用。用慢病毒转染小鼠骨髓间充质干细胞（mBMSC）以产生Foxq 1过表达mBMSC、Foxq 1抑制mBMSC和mBMSC对照。用茜素红染色、碱性磷酸酶活性测定和RT-qPCR检测成骨分化活性。通过TOPFlash/FOPFlash测定、免疫荧光染色和β-catenin（CTNNB 1）的western blot测定来比较各组之间的Wnt/β-catenin信号传导活性。还进行了免疫共沉淀质谱法以鉴定与FOXQ 1结合的蛋白质。FOXQ 1的表达与骨髓间充质干细胞的成骨分化呈正相关。FOXQ 1还促进了CTNNB 1在mBMSCs中的核转位，增强了Wnt/β-catenin信号传导，这也被证明是FOXQ 1在mBMSCs中的成骨分化促进作用所必需的。膜联蛋白A2（ANXA 2）与FOXQ 1结合，其缺失逆转了FOXQ 1对Wnt/β-catenin信号传导的促进作用。这些结果表明，FOXQ 1与ANXA 2结合，促进骨髓间充质干细胞中的Wnt/β-catenin信号传导，随后促进成骨分化。
This study investigated the role of Forkhead box Q1 (FOXQ1) in the osteogenic differentiation of bone mesenchymal stem cells. Mouse bone mesenchymal stem cells (mBMSCs) were transfected with lentivirus to generate Foxq1-overexpressing mBMSCs, Foxq1-suppressed mBMSCs, and mBMSC controls. The activity of osteogenic differentiation was evaluated with alizarin red staining, alkaline phosphatase activity assay, and RT-qPCR. Wnt/β-catenin signaling activities were compared among groups by TOPFlash/FOPFlash assay, immunofluorescence staining, and western blot assay of beta-catenin (CTNNB1). Coimmunoprecipitation mass spectrometry was also carried out to identify proteins binding with FOXQ1. Our data showed that FOXQ1 expression was positively correlated with the osteogenic differentiation of the mBMSCs. FOXQ1 also promoted the nuclear translocation of CTNNB1 in the mBMSCs, enhancing Wnt/β-catenin signaling, which was also shown to be essential for the osteogenic differentiation-promoting effect of FOXQ1 in the mBMSCs. Annexin A2 (ANXA2) was bound with FOXQ1, and its depletion reversed the promoting effect of FOXQ1 on Wnt/β-catenin signaling. These results showed that FOXQ1 binds with ANXA2, promoting Wnt/β-catenin signaling in bone mesenchymal stem cells, which subsequently promotes osteogenic differentiation.