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Irisin promotes osteogenic differentiation of bone marrow mesenchymal stem cells by activating autophagy via the Wnt//β-catenin signal pathway
Cytokine ( IF 3.8 ) Pub Date : 2020-12-01 , DOI: 10.1016/j.cyto.2020.155292
Xi Chen 1 , Kening Sun 2 , Sijia Zhao 3 , Tianxiang Geng 1 , Xin Fan 1 , Shouxuan Sun 2 , Mengxue Zheng 1 , Qunhua Jin 2
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Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a crucial role in osteoporosis. Irisin, an exercise-induced muscle-dependent myokine, has been reported to stimulate the development of brown adipose tissue and regulate energy expenditure. The present study aimed to investigate the effects of irisin on autophagy in BMSCs. Furthermore, the osteogenic differentiation ability was evaluated, as well as the activation of autophagy. It was found that 40 μM irisin for 48 h was an appropriate concentration and time period, with regards to cell viability, which was measured with a Cell Counting Kit-8. Moreover, the increasing expression levels of microtubule-associated protein light chain 3 (Lc3)-I/II and autophagy related 5 (Atg5) by irisin demonstrated the upregulation of autophagy. Mechanistically, bafilomycin A1 and Atg5 small interfering RNA were used to evaluate the possible mechanism of autophagy activated by irisin, and it was identified that irisin may upregulate autophagy by increasing the Atg12-Atg5-Atg16L complex. In addition, with the increasing level of autophagy, osteogenesis and the Wnt/β-catenin signal pathway were also enhanced. However, inhibition of autophagy by bafilomycin A1 negatively regulated osteogenic differentiation. Collectively, the present results suggested that irisin may stimulate autophagy in BMSCs and that osteogenic differentiation may be enhanced by stimulating autophagy.

中文翻译:

鸢尾素通过Wnt//β-catenin信号通路激活自噬促进骨髓间充质干细胞成骨分化

骨髓间充质干细胞 (BMSCs) 的成骨分化在骨质疏松症中起着至关重要的作用。据报道,鸢尾素是一种运动诱导的肌肉依赖性肌因子,可刺激棕色脂肪组织的发育并调节能量消耗。本研究旨在研究鸢尾素对 BMSCs 自噬的影响。此外,还评估了成骨分化能力以及自噬的激活。发现 40 μM 鸢尾素 48 小时是合适的浓度和时间段,就细胞活力而言,这是用 Cell Counting Kit-8 测量的。此外,鸢尾素增加的微管相关蛋白轻链 3 (Lc3)-I/II 和自噬相关蛋白 5 (Atg5) 的表达水平证明了自噬的上调。从机制上讲,bafilomycin A1 和 Atg5 小干扰 RNA 用于评估鸢尾素激活自噬的可能机制,并确定鸢尾素可能通过增加 Atg12-Atg5-Atg16L 复合物来上调自噬。此外,随着自噬水平的提高,成骨和Wnt/β-catenin信号通路也增强。然而,巴弗洛霉素 A1 对自噬的抑制负向调节成骨分化。总的来说,目前的结果表明鸢尾素可以刺激 BMSCs 中的自噬,并且可以通过刺激自噬来增强成骨分化。随着自噬水平的提高,成骨和 Wnt/β-catenin 信号通路也增强。然而,巴弗洛霉素 A1 对自噬的抑制负向调节成骨分化。总的来说,目前的结果表明鸢尾素可以刺激 BMSCs 中的自噬,并且可以通过刺激自噬来增强成骨分化。随着自噬水平的提高,成骨和 Wnt/β-catenin 信号通路也增强。然而,巴弗洛霉素 A1 对自噬的抑制负向调节成骨分化。总的来说,目前的结果表明鸢尾素可以刺激 BMSCs 中的自噬,并且可以通过刺激自噬来增强成骨分化。
更新日期:2020-12-01
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