负载激活的FGFR和β1整合素准不同的冠状细胞机械反应基因
Helen F Dietmar1, Pia A Weidmann1, Paolo Alberton2
1Experimental Orthopaedics, Research Centre for Molecular and Regenerative Orthopaedics, Department of Orthopaedics, Heidelberg University Hospital, Heidelberg, Germany.
概括
机械负荷通过多个受体激活肌肉细胞,包括FGF/FGFR信号和β1整合素. 这项研究为每个途径确定了不同的基因,为骨关节炎提供了新的治疗策略.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 生物材料科学 生物材料科学
背景情况:
- 冠状细胞通过改变基因表达来响应机械刺激,但具体的途径和涉及的基因尚未完全理解.
- 目前尚不清楚由机械负荷激活的不同细胞表面受体是否汇聚到相同的机械反应基因上或调节不同的组.
研究的目的:
- 为了研究负载激活的FGF/FGFR信号和β1整合素是否激活ERK,并控制体细胞中相同或不同的机械调节基因子集.
- 为了定义通路特定的基因目标在肌肉细胞的机械负荷.
主要方法:
- 组织工程新软骨是由小鼠和人类软骨细胞创建的.
- 动态不受限制的压缩应用与或没有FGFR抑制.
- 来自β1整合素缺陷和野生类型冠状细胞的新软骨被用于评估β1整合素的作用.
主要成果:
- 负载激活的FGFR信号诱导了在小鼠冠状细胞和部分在人类冠状细胞中的ERK激活.
- 观察到不同的基因表达模式:FGFR调节了Fosl1,Itga5,Ngf和Timp1 (取决于发育阶段),而β1整基因控制了Inhba表达.
- 在人体冠状细胞中,FGFR信号调节了BMP2,PTGS2和DUSP5,但不是FOSB.
结论:
- 冠状细胞对机械负荷的反应是由多个受体的同时激活协调的.
- 首次确定了激活FGFR和β1整合素通路的明确向基因.
- 这些发现为药理学调节状细胞机械反应提供了基础,在骨关节炎管理和治疗开发方面有潜在的应用.
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