The General Hospital of Ningxia Medical University, Yinchuan, China.
Orthopedics Ward 3, The General Hospital of Ningxia Medical University, Yinchuan, China.
Stem Cells Dev. 2021 Jan 15;30(2):106-117. doi: 10.1089/scd.2020.0165. Epub 2020 Dec 17.
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.
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。