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.

中文翻译：

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CircRNA hsa_circ_0074834通过充当miR-942-5p的ceRNA来促进骨间充质干细胞（BMSC）中的成骨-血管生成偶联过程。

骨组织具有很强的自我修复能力。如果治疗得当，大多数骨折都可以he愈。但是，有些骨折很难愈合。当骨折不愈合时，称为骨不连。大约所有骨折患者中有5％难以康复。由于骨折部位的连续运动，骨骨不连通常伴有疼痛，这大大降低了患者的生活质量。骨髓间充质干细胞（BMSC）在骨不连过程中起重要作用。环状RNA（circRNA）是一种独特的非编码RNA，代表了RNA领域的最新研究热点。目前，尚无研究报道circRNA在骨不连发展中的作用。从骨不连的患者中分离出骨髓间充质干细胞后，通过使用circRNA芯片检测circRNA在这些细胞中的表达。碱性磷酸酶和茜素红染色被用来检测hsa_circ_0074834对骨髓间充质干细胞成骨分化的调控。hsa_circ_0074834的靶基因通过RNA下拉和双荧光素酶报告基因检测。hsa_circ_0074834在体内调节BMSCs成骨的能力通过异位成骨和单个皮质骨缺损实验进行了测试。结果表明，骨不连接患者骨髓间充质干细胞中hsa_circ_0074834的表达降低。Hsa_circ_0074834充当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。