Department of Surgery, Ningxia Medical University, Yinchuan, Ningxia 750004, China.
Department of Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
Cytokine. 2020 Dec;136:155292. doi: 10.1016/j.cyto.2020.155292. Epub 2020 Sep 17.
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.
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。鸢尾素是一种运动诱导的肌肉依赖性肌因子，据报道可刺激棕色脂肪组织的发育并调节能量消耗。本研究旨在探讨鸢尾素对 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情况。结果发现，40μM 鸢尾素作用 48h 是一个合适的细胞活力浓度和时间，这是通过细胞计数试剂盒-8 测量的。此外，鸢尾素使微管相关蛋白轻链 3（Lc3）-I/II 和自噬相关 5（Atg5）的表达水平增加，表明自噬的上调。从机制上讲，使用巴弗洛霉素 A1 和 Atg5 小干扰 RNA 来评估鸢尾素激活自噬的可能机制，结果表明鸢尾素可能通过增加 Atg12-Atg5-Atg16L 复合物来上调自噬。此外，随着自噬水平的增加，成骨和 Wnt/β-catenin 信号通路也得到增强。然而，巴弗洛霉素 A1 抑制自噬会负调控成骨分化。总之，本研究结果表明，鸢尾素可能刺激 BMSCs 中的自噬，并且通过刺激自噬可能增强成骨分化。
