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内源硫化通过Ca2+/ERK通路增强的异常骨质活动加速了创伤诱导的异型骨化
Zhengqiang Yuan1, Juehong Li1, Kuangyu He1
1Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, PR China; Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai 200233, PR China; Youth Science and Technology Innovation Studio of Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
硫化 (H2S) 积累通过激活肌衍生干细胞,促进创伤诱导的异型骨化 (tHO). 抑制H2S生产或使用氧化纳米颗粒有效地阻止了tHO的形成.
科学领域:
- 生物医学工程 生物医学工程
- 干细胞生物学 干细胞生物学
- 分子生物学分子生物学
背景情况:
- 创伤诱导的异型骨化 (tHO) 由于不有效的治疗方法,带来了重大的临床挑战.
- 硫化 (H2S) 是一种气体传递物,在干细胞命运的决定中起着至关重要的作用,这表明它参与了tHO的致病性.
研究的目的:
- 阐明H2S在tHO的发展中的机制.
- 探索针对H2S进行tHO治疗的潜在治疗策略.
主要方法:
- 研究了H2S的产生及其对肌损伤后肌衍生干细胞 (TDSC) 的影响.
- 利用RNA测序和救援实验来识别下游的信号通路.
- 评估的氧化纳米颗粒 (ZnO),包括性变体 (D-ZnO,L-ZnO,R-ZnO),用于H2S清理和tHO抑制.
主要成果:
- 硫代谢酶的增强表达导致tHO区域的H2S积累.
- 内源H2S促进了TDSCs的骨质分化,加速了tHO的形成.
- 抑制H2S生产或清理H2S取消了骨质诱导和tHO.
- H2S诱导的骨质生成承诺和tHO是由Ca2+/ERK通路调解的.
- ZnO纳米粒子,特别是D-ZnO和L-ZnO,通过清除H2S有效地抑制了tHO.
结论:
- 内生H2S信号传递是tHO发育中的关键机制.
- 向H2S生产或清除H2S为tHO提供了一个有前途的治疗策略.
- 氧化纳米颗粒为临床tHO治疗提供了一个可行的平台.
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