Diabetic osteoporosis (DOP) is attributed to the aberrant physiological function of bone marrow mesenchymal stem cells (BMSCs) under high glucose (HG) environment. MicroRNAs (miRNAs) are involved in the pathological processes of DOP. We aimed to explore the underlying mechanism of miRNA in DOP. BMSCs were cultured in osteogenic medium with HG to induce osteogenic differentiation, and the interaction between miR-493-5p and ZEB2 was assessed by luciferase assay. Herein, we found miR-493-5p is gradually reduced during osteogenic differentiation in BMSCs. HG treatment inhibits osteogenic differentiation and induces an up-regulation of miR-493-5p leading to reduced level of its downstream target ZEB2. Inhibition of miR-493-5p attenuates HG-induced osteogenic differentiation defects by upregulation of ZEB2. Mechanistically, miR-493-5p/ZEB2 signalling mediates HG-inhibited osteogenic differentiation by inactivation of Wnt/β-catenin signalling. More importantly, knockdown of miR-493-5p therapeutically alleviated the DOP condition in mice. HG prevents BMSCs osteogenic differentiation via up-regulation of miR-493-5p, which results in reduced level of ZEB2 by directly targeting its 3′-untranslated region of mRNA. Thus, miR-493-5p/ZEB2 is a potential therapeutic target and provides novel strategy for the treatment and management of DOP.

中文翻译：

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高糖通过调节miR-493-5p / ZEB2信号传导抑制骨髓间充质干细胞的成骨分化。

糖尿病性骨质疏松症（DOP）归因于高葡萄糖（HG）环境下骨髓间充质干细胞（BMSC）的异常生理功能。MicroRNA（miRNA）参与DOP的病理过程。我们旨在探索DOP中miRNA的潜在机制。在具有HG的成骨培养基中培养BMSC以诱导成骨分化，并通过荧光素酶测定评估miR-493-5p和ZEB2之间的相互作用。在本文中，我们发现在骨髓间充质干细胞的成骨分化过程中，miR-493-5p逐渐降低。HG处理抑制成骨细胞分化并诱导miR-493-5p上调，从而导致其下游靶ZEB2水平降低。通过上调ZEB2，抑制miR-493-5p可减轻HG诱导的成骨分化缺陷。机械上，miR-493-5p / ZEB2信号传导通过Wnt /β-catenin信号传导失活介导HG抑制的成骨分化。更重要的是，敲低miR-493-5p在治疗上可减轻小鼠的DOP病状。HG通过上调miR-493-5p阻止BMSC的成骨分化，这通过直接靶向其3'-非翻译mRNA区域导致ZEB2水平降低。因此，miR-493-5p / ZEB2是潜在的治疗靶点，并为DOP的治疗和管理提供了新的策略。通过直接靶向mRNA的3'-非翻译区导致ZEB2的水平降低。因此，miR-493-5p / ZEB2是潜在的治疗靶点，并为DOP的治疗和管理提供了新的策略。通过直接靶向mRNA的3'-非翻译区，导致ZEB2的水平降低。因此，miR-493-5p / ZEB2是潜在的治疗靶点，并为DOP的治疗和管理提供了新的策略。