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从运动中获得的虹膜素通过Nrf2激活和抑制STING/NF-κB信号传递来防止骨质损失
Xinli Hu1, Haojie Zhang1, Zheng Wang2
1Department of Orthopedics, Xuanwu Hospital, Capital Medical University, No.45 Changchun Street, Xicheng District, Beijing, 100053, China; National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China; Laboratory for Clinical Medicine, Capital Medical University, Beijing, China.
运动中产生的肌素 - - 虹膜素通过抑制骨再吸收来对抗骨质疏松症. 这项研究揭示了Irisin-Nrf2-STING/NF-κB信号保护对抗雌激素缺乏的骨质损失.
科学领域:
- 骨生物学和内分泌学
- 细胞信号传输和分子机制
背景情况:
- 骨质疏松症的特点是骨质细胞过度活跃,导致骨质损失.
- 素,一种肌素,涉及到骨重塑,但其在骨质细胞形成中的确切作用尚不清楚.
研究的目的:
- 为了调查伊丽素是否能保护人免受雌激素缺乏引起的骨损失.
- 阐明依赖于虹膜素对骨质细胞形成的影响的分子机制.
主要方法:
- 对绝经后妇女的临床分析,对骨髓衍生的巨体的体外研究,以及使用卵巢切除 (OVX) 鼠标模型的体内研究.
- 使用了网络药理学,分子对接,CETSA,共免疫沉和免疫光测试.
- 研究包括了缺乏Nrf2的小鼠,以确认该机制.
主要成果:
- 在女性中,循环中的虹膜素与骨矿物质密度正相关,与骨再吸收标志物相反相关.
- 虹膜素抑制了RANKL诱导的骨质细胞分化和活性在体外.
- 虹膜素稳定了Nrf2,抑制了TRAF6介导的STING激活和下游NF-κB信号传递.
- 虹膜素的使用改善了OVX小鼠的骨微架构,这种效果取决于Nrf2.
结论:
- 一个虹膜素-Nrf2-STING/NF-κB信号轴抑制骨质细胞生成.
- 虹膜素通过这种途径缓解雌激素缺乏引起的骨损失.
- 虹膜素代表了对骨质疏松症的潜在治疗剂.
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