CircRNA hsa_circ_0074834 promotes the osteogenesis-angiogenesis coupling process in bone mesenchymal stem cells (BMSCs) by acting as a ceRNA for miR-942-5p
CircRNA hsa_circ_0074834 promotes the osteogenesis-angiogenesis coupling process in bone mesenchymal stem cells (BMSCs) by acting as a ceRNA for miR-942-5p
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CircRNA hsa_circ_0074834 通过充当 miR-942-5p 的 ceRNA 促进骨间充质干细胞 (BMSC) 中的成骨-血管生成偶联过程
DOI：
10.1038/s41419-019-2161-5
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发表时间：
2019-12-05
影响因子：
9
通讯作者：
Liu, Tang
中科院分区：
文献类型：
--
作者：
Ouyang, Zhengxiao;Tan, Tingting;Liu, Tang
骨组织具有很强的自我修复能力。如果治疗得当，大多数骨折都会愈合良好。然而，有些骨折很难愈合。当骨折不愈合时，称为骨不连。大约 5% 的骨折患者难以愈合。由于骨折部位不断移动，骨不连通常伴有疼痛，大大降低了患者的生活质量。骨髓间充质干细胞（BMSC）在骨不连过程中发挥着重要作用。环状RNA（circRNA）是一类独特的非编码RNA，代表了RNA领域的最新研究热点。目前，尚无研究报道circRNA在骨不连发生中的作用。从骨不连患者分离BMSC后，使用circRNA微阵列检测这些细胞中circRNA的表达。采用碱性磷酸酶和茜素红染色检测hsa_circ_0074834对BMSCs成骨分化的调节作用。通过RNA pull-down和双荧光素酶报告基因检测检测hsa_circ_0074834的靶基因。通过异位成骨和单一皮质骨缺损实验测试了hsa_circ_0074834在体内调节BMSC成骨的能力。结果显示骨不连患者的BMSCs中hsa_circ_0074834的表达降低。 Hsa_circ_0074834 作为 ceRNA 通过 microRNA-942-5p 调节 ZEB1 和 VEGF 的表达。 Hsa_circ_0074834可以促进BMSC的成骨分化和骨缺损的修复。这些结果表明，circRNA可能是治疗骨不连的关键靶点。
Bone tissue has a strong ability to repair itself. When treated properly, most fractures will heal well. However, some fractures are difficult to heal. When a fracture does not heal, it is called nonunion. Approximately, 5% of all fracture patients have difficulty healing. Because of the continuous movement of the fracture site, bone nonunion is usually accompanied by pain, which greatly reduces the quality of life of patients. Bone marrow mesenchymal stem cells (BMSCs) play an important role in the process of nonunion. Circular RNAs (circRNAs) are a unique kind of noncoding RNA and represent the latest research hotspot in the RNA field. At present, no studies have reported a role of circRNAs in the development of nonunion. After isolation of BMSCs from patients with nonunion, the expression of circRNAs in these cells was detected by using a circRNA microarray. Alkaline phosphatase and Alizarin red staining were used to detect the regulation of osteogenic differentiation of BMSCs by hsa_circ_0074834. The target gene of hsa_circ_0074834 was detected by RNA pull-down and double-luciferase reporter assay. The ability of hsa_circ_0074834 to regulate the osteogenesis of BMSCs in vivo was tested by heterotopic osteogenesis and single cortical bone defect experiments. The results showed that the expression of hsa_circ_0074834 in BMSCs from patients with nonunion was decreased. Hsa_circ_0074834 acts as a ceRNA to regulate the expression of ZEB1 and VEGF through microRNA-942-5p. Hsa_circ_0074834 can promote osteogenic differentiation of BMSCs and the repair of bone defects. These results suggest that circRNAs may be a key target for the treatment of nonunion.