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SDF-1α 通过 Wnt/β-连环蛋白通路促进小鼠骨髓间充质干细胞的迁移、增殖和成骨分化。

SDF Factor-1α Promotes the Migration, Proliferation, and Osteogenic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells Through the Wnt/β-Catenin Pathway.

机构信息

The General Hospital of Ningxia Medical University, Yinchuan, China.

Orthopedics Ward 3, The General Hospital of Ningxia Medical University, Yinchuan, China.

出版信息

Stem Cells Dev. 2021 Jan 15;30(2):106-117. doi: 10.1089/scd.2020.0165. Epub 2020 Dec 17.

Abstract

Bone marrow mesenchymal stem cells (BMSCs) are thought to have great potential in the treatment of many diseases and may serve as a cell source for tissue engineering. These cells may be regulated by stromal cell-derived factor-1α (SDF-1α), which has been shown to promote the migration, proliferation, and osteogenic differentiation of BMSCs in inflammation-associated diseases. However, the specific mechanism underlying this process remains unclear. We herein transduced lentivirus carrying SDF-1α, empty vector, or siRNA-SDF-1α into mouse BMSCs and then performed transwell, CCK-8, cell cycle, alkaline phosphatase activity, and Alizarin Red staining experiments on the three groups of samples. Overexpression of SDF-1α promoted the migration, proliferation, and osteogenic differentiation of BMSCs, and SDF-1α upregulated the expression of Wnt pathway-related factors and downstream target genes as determined by western blot, real-time polymerase chain reaction, and immunofluorescence. The effect of low SDF-1α expression on BMSCs was significantly weakened. In addition, we transduced lentivirus carrying siRNA-Wnt3a into BMSCs and treated them with SDF-1 drugs. After inhibiting the Wnt pathway, SDF-1 significantly weakened the migration, proliferation, and osteogenic differentiation of BMSCs. From this, we concluded that high SDF-1 expression can promote the migration, proliferation, and osteogenic differentiation of BMSCs, at least in part by activating the Wnt pathway.

摘要

骨髓间充质干细胞(BMSCs)被认为在治疗许多疾病方面具有巨大潜力,并且可能作为组织工程的细胞来源。基质细胞衍生因子-1α(SDF-1α)可以调节这些细胞,它已被证明可以促进炎症相关疾病中 BMSCs 的迁移、增殖和成骨分化。然而,这一过程的具体机制尚不清楚。我们将携带 SDF-1α 的慢病毒、空载体或 siRNA-SDF-1α 转染到小鼠 BMSCs 中,然后对三组样本进行 Transwell、CCK-8、细胞周期、碱性磷酸酶活性和茜素红染色实验。SDF-1α 的过表达促进了 BMSCs 的迁移、增殖和成骨分化,Western blot、实时聚合酶链反应和免疫荧光检测结果表明 SDF-1α 上调了 Wnt 通路相关因子及其下游靶基因的表达。低 SDF-1α 表达对 BMSCs 的作用明显减弱。此外,我们将携带 siRNA-Wnt3a 的慢病毒转染到 BMSCs 中,并对其进行 SDF-1 药物处理。抑制 Wnt 通路后,SDF-1 明显减弱了 BMSCs 的迁移、增殖和成骨分化。由此我们得出结论,高 SDF-1 表达可以促进 BMSCs 的迁移、增殖和成骨分化,至少部分是通过激活 Wnt 通路。

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