核因子-卡帕B 骨质细胞生成和骨质母细胞生成的调节
Brendan F Boyce1,2, Jinbo Li1,2, Zhenqiang Yao1,2
1Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Endocrinology and metabolism (Seoul, Korea)
|September 26, 2023
概括
核因子-kappa B (NF-κB) 信号通过控制骨质细胞和骨质细胞活动来调节骨重塑. 准TRAF3信号可能提供一种治疗策略,以对抗与年龄相关的骨质损失和骨质疏松症.
科学领域:
- 骨生物学和骨重塑.
- 细胞信号通路在骨质恒温. 细胞信号通路在骨质恒温.
- 与年龄相关的骨疾病和治疗目标.
背景情况:
- 骨完整性依赖于平衡的骨质细胞和骨质细胞活动.
- 核因子-kappa B (NF-κB) 信号传递对于调节骨细胞的形成和功能至关重要.
- 像RANKL和TNF这样的细胞因子激活NF-κB,影响骨质细胞形成和骨质细胞形成.
研究的目的:
- 阐明NF-κB信号在细胞因子介导的骨质细胞和骨质细胞调节中的双重作用.
- 突出TNF受体相关因子3 (TRAF3) 在骨重塑中的特定作用.
- 探索针对TRAF3增强骨质的治疗策略.
主要方法:
- 在骨质细胞和骨质细胞前体中研究NF-κB信号通路.
- 分析TRAF3在调节骨质细胞和骨质细胞形成中的作用.
- 评估骨髓中性粒细胞与年龄相关的变化及其对骨质的影响.
- 在老年小鼠中使用马拉维罗克对CCR5抑制的评估.
主要成果:
- TRAF6调解了RANKL诱导的骨质细胞形成,而TRAF3限制了骨质细胞形成和TGFβ诱导的骨质细胞形成抑制.
- 衰老会增加表达TGFβ和CCR5的骨髓中性粒细胞,这与通过TRAF3降解减少骨质量有关.
- 在老年小鼠中,马拉维洛克治疗减少了中性粒细胞的积累,抑制了骨质再吸收,增加了骨质形成,从而增加了骨质量.
结论:
- NF-κB信号通路,特别是涉及TRAF3,在骨重塑中起着复杂的作用.
- 与年龄相关的骨质疏松症与TGFβ诱导的TRAF3降解和增加的炎症性中性粒细胞有关.
- 例如,通过抑制CCR5来准TRAF3信号,为治疗与年龄相关的骨质损失提供了一个有前途的治疗途径.
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