首页> 美国卫生研究院文献>Aging (Albany NY) >CircRNA hsa_circ_0006215 promotes osteogenic differentiation of BMSCs and enhances osteogenesis–angiogenesis coupling by competitively binding to miR-942-5p and regulating RUNX2 and VEGF
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CircRNA hsa_circ_0006215 promotes osteogenic differentiation of BMSCs and enhances osteogenesis–angiogenesis coupling by competitively binding to miR-942-5p and regulating RUNX2 and VEGF

机译:CircRNA HSA_CIRC_0006215促进BMSC的成骨分化并通过竞争性结合MIR-942-5P和调节RUNX2和VEGF来增强成骨血管生成偶联

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摘要

Coupling between osteogenesis and angiogenesis determines bone morphology. A decrease in the osteogenic ability of bone marrow mesenchymal stem cells (BMSCs) is one of the underlying causes of senile osteoporosis (OP). Here, we investigated the involvement of circular RNAs (circRNAs) in the osteogenic differentiation of BMSCs and the pathogenesis of senile OP. We sequenced RNA and found decreases expression of hsa_circ_0006215 in BMSCs from patients with OP. We further assessed the role of hsa_circ_0006215 in the osteogenic differentiation of BMSCs using lentivirus-mediated hsa_circ_0006215 overexpression and knockdown. Overexpression of hsa_circ_0006215 promoted the osteogenic differentiation of BMSCs. Luciferase reporter and RNA pull-down assays revealed that hsa_circ_0006215 bound to miRNA-942-5p and thus regulated RUNX2 and vascular endothelial growth factor (VEGF) expression in BMSCs. We assessed osteogenesis and vascular coupling in co-cultured cells, and the role of hsa_circ_0006215 in bone formation in vivo using a cortical bone defect model. We found that hsa_circ_0006215 promoted bone defect repair. Overall, our results showed that hsa_circ_0006215 has an important function in osteogenesis and could be a novel target for treating senile OP.
机译:骨发生与血管生成之间的偶联决定了骨形态。骨髓间充质干细胞(BMSCs)的成骨能力的降低是老年骨质疏松症(OP)的潜在原因之一。在这里,我们调查了圆形RNA(Circrnas)在BMSCs的骨质发生分化中的参与和老年op的发病机制。我们测序RNA,发现来自OP患者的BMSCS中HSA_CIRC_0006215的表达。我们进一步评估了HSA_CIRC_0006215使用慢病毒介导的HSA_CIRC_0006215过表达和敲低的BMSCs对BMSCs的成骨分化的作用。 HSA_CIRC_0006215的过表达促进了BMSC的骨质发生分化。荧光素酶报告器和RNA下拉测定显示HSA_CIRC_0006215与miRNA-942-5P结合,并因此在BMSC中进行调节的RUNX2和血管内皮生长因子(VEGF)表达。我们评估了共培养细胞中的成骨和血管偶联,以及使用皮质骨缺陷模型在体内骨形成中的HSA_CIRC_0006215的作用。我们发现HSA_CIRC_0006215促进了骨缺陷修复。总体而言,我们的结果表明,HSA_CIRC_0006215在骨开发中具有重要功能,并且可以成为治疗老年妇女的新靶点。

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