从骨细胞中释放的CXCL10在对TNF-α刺激的反应中对骨质细胞的作用
Mariko Miura1, Hideki Kitaura2, Fumitoshi Ohori1
1Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
Scientific reports
|January 24, 2025
概括
瘤坏死因子-α (TNF-α) 通过增加骨细胞中的CXCL10,促进骨质细胞前体迁移和骨质损失,从而推动骨质再吸收. 中和CXCL10可以减少这些影响.
科学领域:
- 骨生物学 骨生物学 骨生物学
- 炎症 炎症是一种炎症.
- 细胞因子信号传递
背景情况:
- 瘤亡因子-α (TNF-α) 是炎症条件下的骨再吸收的关键调节者.
- 通过TNF-α影响骨细胞和骨代谢的特定机制尚未完全理解.
研究的目的:
- 阐明TNF-α在骨细胞功能中的作用及其对骨再吸收的影响.
- 研究TNF-α刺激在骨细胞的下游效应,特别是化学激素的表达.
- 在体内确定TNF-α诱导因素对骨质细胞形成和骨质损失的贡献.
主要方法:
- 通过细胞分类从DMP1-Topaz小鼠中分离高度净化的骨细胞.
- RNA测序 (RNA-seq) 用于分析在TNF-α刺激后骨细胞中的基因表达变化.
- 在体外测试包括骨质细胞分化,共同培养系统和跨井迁移测试.
- 在体内研究涉及TNF-α和CXCL10中和抗体在小鼠的上注射.
- 在经过治疗的骨中评估骨质细胞形成和骨质再吸收.
主要成果:
- TNF-α刺激显著增加了骨细胞中的C-X-C动机化学因联体10 (CXCL10) 基因表达.
- 虽然CXCL10没有直接影响骨质细胞分化,但它增强了骨质细胞前体的迁移.
- 在体外,TNF-α诱导的骨质细胞前体迁移被CXCL10.10部分调解.
- 在体内,TNF-α的使用增加了CXCL10阳性骨质细胞,骨质细胞形成和骨质再吸收.
- 用CXCL10中和抗体治疗显著降低了TNF-α诱导的骨质细胞形成和骨质再吸收.
结论:
- 在骨细胞中,TNF-α诱导CXCL10的表达.
- 骨细胞衍生的CXCL10在增强骨质细胞前体迁移方面发挥作用.
- 这种CXCL10介导的机制有助于TNF-α诱导的骨质细胞形成和随后的骨质再吸收 in vivo.
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