由ITAM动机介导的成本刺激信号与RANKL合作,促进骨质恒温
Takako Koga1, Masanori Inui, Kazuya Inoue
1Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Nature
|April 16, 2004
概括
免疫系统适配器Fc受体常见马子单元 (FcRgamma) 和DNAX激活蛋白 (DAP) 12对于骨健康至关重要. 它们的缺失损害了骨质细胞分化,突出了它们在维持骨平衡中的重要作用.
科学领域:
- 免疫学 免疫学 免疫学
- 骨生物学 骨生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 辅助刺激信号对于免疫细胞激活至关重要,但它们在其他生物系统 (如骨发育) 中的作用不太清楚.
- 骨稳定依赖于骨形成和再吸收之间的平衡,NF-kappaB联结体 (RANKL) 的受体激活器调节骨质细胞分化.
研究的目的:
- 为了研究免疫受体氨酸基激活动机 (ITAM) 寄存适配器在骨生物学中的作用.
- 为了阐明参与骨质结晶发生的信号通路,除了RANKL和M-CSF刺激.
主要方法:
- 对缺乏Fc受体常见马子单元 (FcRgamma) 和DNAX激活蛋白 (DAP) 的小鼠的分析12.
- 研究骨质细胞前体细胞中的信号激活.
- 评估骨质细胞分化和骨质稳定.
主要成果:
- 缺乏FcRgamma和DAP12的小鼠由于骨质细胞分化受损而表现出严重的骨质疏松症.
- 发现FcRgamma和DAP12与免疫受体结合,并在骨质前体前体中通过脂酶Cgamma激活信号传递.
- 这些发现表明,单独RANKL和M-CSF对骨质结晶发生信号不够.
结论:
- 由FcRgamma和DAP12介导的依赖ITAM的辅助刺激信号对于骨质稳定至关重要.
- 多个免疫受体通过依赖ITAM的信号通路对骨维护有所贡献.
- 这项研究揭示了辅助刺激信号在骨生物学中的新角色,独立于以前已知的途径.
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