辐射通过激活STING-TBK1通路诱导骨微环境的破坏
Yuyang Wang1,2, Li Ren1, Linshan Xu1
1Institute of Radiation Medicine, Fudan University, 2094 Xietu Road, Shanghai 200032, China.
Medicina (Kaunas, Lithuania)
|July 29, 2023
概括
辐射通过STING-P-TBK1通路破坏微环境,从而损害骨,导致骨质损失. 用STING抗剂抑制这种途径可以修复损伤并恢复骨平衡.
科学领域:
- 骨生物学 骨生物学 骨生物学
- 放射治疗研究 放射治疗研究
- 细胞信号传输 细胞信号传输
背景情况:
- 治疗性辐射 (IR) 可以损害正常的骨组织,导致骨损失和促进瘤转移.
- 红外线引起的骨微环境的破坏是一个重要的临床问题.
- 了解细胞机制对于预防放射治疗相关的不良影响至关重要.
研究的目的:
- 探索红外激光诱导的骨微环境破坏的细胞调节机制.
- 为了研究干扰素基因刺激器 (STING) 途径在辐射诱导的骨损伤中的作用.
- 为了确定潜在的治疗目标,以减轻放射治疗相关的骨损失.
主要方法:
- 已建立的局部IR小鼠模型和体外骨细胞 (OCY) 模型.
- 分析了辐射后的多细胞生物损伤和细胞衰老.
- 利用小干扰RNA (siRNA) 和一种STING抑制剂 (C-176) 来探测STING通路的作用.
主要成果:
- 局部IR诱导的OCY功能障碍,骨质细胞生成激活,骨质生成退化和细胞衰老.
- 辐射显著提高了STING表达,P-TBK1,RANKL和SOST水平.
- 通过siRNA或C-176的STING抑制减轻了IR诱导的骨质结晶形成,并防止骨损伤.
结论:
- 在IR诱导的骨微环境中,STING-P-TBK1信号通路对于调节炎性细胞因子分泌和骨质细胞形成至关重要.
- 选择性STING抗体显示出修复IR诱导的多细胞损伤和重新平衡骨代谢的潜力.
- 针对STING通路提供了一种有希望的策略,以防止放射治疗对骨的不良影响.
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