通过FNIP1-TFEB-IGF2轴的肌肉骨交叉对话与人类和小鼠的骨代谢有关
Yan Mao1, Zhen Jin2,3, Jing Yang1
1State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Jiangsu Key Laboratory of Molecular Medicine, Chemistry and Biomedicine Innovation Center (ChemBIC), Medical School of Nanjing University, Nanjing University, Nanjing 210061, China.
Science translational medicine
|June 5, 2024
概括
肌肉功能障碍通过降低毛囊素相互作用蛋白1 (FNIP1) 导致骨质损失. 这导致胰岛素类生长因子2 (IGF2) 的增加,该因子会降解骨,突出了骨质疏松症的新治疗点.
科学领域:
- 生物医学科学 生物医学科学
- 肌肉骨研究 研究
- 分子生物学分子生物学
背景情况:
- 临床观察将肌肉功能障碍与骨质损失联系起来,但机制尚不清楚.
- 肢体带肌肉缩症患者在肌肉中表现出毛囊素相互作用蛋白1 (FNIP1) 的减少.
- FNIP1涉及肌肉和骨的交叉声调.
研究的目的:
- 阐明将肌肉功能障碍与骨质损失联系起来的分子机制.
- 为了研究FNIP1在肌肉骨交音中的作用.
- 确定骨质疏松症和肌肉骨疾病的潜在治疗点.
主要方法:
- 使用了人类患者数据和小鼠遗传模型 (功能增加和丧失).
- 在缺乏FNIP1的小鼠中评估骨质量,骨质细胞活性和机械特性.
- 研究了转录因子EB (TFEB) 和胰岛素样生长因子2 (IGF2) 信号通路的作用.
主要成果:
- 在小鼠中,肌肉特异性的FNIP1缺乏导致骨质减少和骨质细胞活性增加.
- 缺乏FNIP1刺激了TFEB的核转移,上调了IGF2的表达和分泌.
- 肌肉衍生的IGF2通过IGF2受体信号传递促进骨质结晶发生,减少骨体积和机械性质.
- 人类骨质疏松症患者的血清IGF2水平与骨健康有负相关性.
结论:
- 与肌肉功能障碍相关的骨损失是由减少的FNIP1表达介导的,导致IGF2.2的增加.
- 肌肉衍生的IGF2作为肌肉骨轴中的关键信号分子.
- 这种FNIP1-IGF2通路代表了治疗骨损失和相关疾病的新治疗标.
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